Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation
Identifieur interne : 001580 ( Istex/Corpus ); précédent : 001579; suivant : 001581Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation
Auteurs : Ortwin Rott ; James J. Mond ; Evelyne CashSource :
- Immunobiology [ 0171-2985 ] ; 1996.
English descriptors
- Teeft :
- Activation, Adsorption values, Antigen organization, Cell activation, Cell activators, Cell encounter, Cell proliferation, Cell proliferative responses, Cell responses, Cell responsiveness, Cell stimulation, Cell subpopulation, Cell subpopulations, Cells cells, Cholera toxin, Clear differences, Cochin hospital, Culture medium, Culture period, Different amounts, Different concentrations, Different forms, First example, Flow cytometry, High amounts, High concentrations, High rate, Immunoglobulin, Immunoglobulin synthesis, Immunol, Independent experiments, Influenza, Influenza virus, Influenza virus glycoprotein hemagglutinin, Influenza virus hemagglutinin, Influenza viruses, Inhibitory, Inhibitory effects, Lymphocyte, Lymphocyte activation, Maximal responses, Measurable production, Molecular strategy, Mond, Murine, Neonatal mice, Obligatory role, Other hand, Pathway, Phorbol esters, Phosphodiesterase inhibitor pentoxifylline, Proliferative, Proliferative responses, Reagent, Receptor, Respective stimulus, Responder cells, Rott, Saline solution, Saturating concentrations, Side scatter parameters, Significant proliferative responses, Similar observations, Small amounts, Soluble, Soluble antibodies, Soluble form, Suboptimal amounts, Subtype virus, Superstimulatory, Superstimulatory function, Superstimulatory influenza virus, Superstimulatory influenza viruses, Superstimulatory protein, Synergistic effects, Transduction, Transduction machinery, Transgenic mice, Triplicate determinations, Virus.
Abstract
Abstract: The influenza virus glycoprotein hemagglutinin (HA) behaves as a superstimulatory protein for B lymphocytes from various species. Polyclonal B cell stimulation mediated by HA can be blocked by soluble anti-Ig antibodies. We here report that, if presented in a highly organized form, i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and peritoneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and vice versa. Similarly, anti-Ig-Dex, which on its own cannot incude Ig production in the absence of added cytokines, significantly enhanced Ig synthesis in response to superstimulatory HA. By contrast, poorly organized BCR-ligands (i.e. the same anti- Ig mAb in a soluble form) had either no, or a strong inhibitory effect on virus-triggered lymphocyte activation. Assays with various second messenger-antagonists, however, revealed clear differences in the signaling pathway employed by anti-Ig-Dex and HA, suggesting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. Taken together, these results indicate that the superstimulatory function of influenza virus HA represents a molecular strategy to mimick B cell activation by conventional, highly organized particulate-antigens.
Url:
DOI: 10.1016/S0171-2985(96)80056-8
Links to Exploration step
ISTEX:A638AD5133DF017B1457D97864A9A8FBBA70D818Le document en format XML
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Polyclonal B cell stimulation mediated by HA can be blocked by soluble anti-Ig antibodies. We here report that, if presented in a highly organized form, i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and peritoneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and vice versa. Similarly, anti-Ig-Dex, which on its own cannot incude Ig production in the absence of added cytokines, significantly enhanced Ig synthesis in response to superstimulatory HA. By contrast, poorly organized BCR-ligands (i.e. the same anti- Ig mAb in a soluble form) had either no, or a strong inhibitory effect on virus-triggered lymphocyte activation. Assays with various second messenger-antagonists, however, revealed clear differences in the signaling pathway employed by anti-Ig-Dex and HA, suggesting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. Taken together, these results indicate that the superstimulatory function of influenza virus HA represents a molecular strategy to mimick B cell activation by conventional, highly organized particulate-antigens.</div></front></TEI><istex><corpusName>elsevier</corpusName><keywords><teeft><json:string>lymphocyte</json:string><json:string>superstimulatory</json:string><json:string>immunol</json:string><json:string>proliferative</json:string><json:string>cell activation</json:string><json:string>transduction</json:string><json:string>rott</json:string><json:string>immunoglobulin</json:string><json:string>pathway</json:string><json:string>murine</json:string><json:string>mond</json:string><json:string>receptor</json:string><json:string>influenza</json:string><json:string>superstimulatory influenza virus</json:string><json:string>inhibitory effects</json:string><json:string>cell stimulation</json:string><json:string>subtype virus</json:string><json:string>cell responses</json:string><json:string>lymphocyte activation</json:string><json:string>cell proliferative responses</json:string><json:string>proliferative responses</json:string><json:string>cell encounter</json:string><json:string>reagent</json:string><json:string>soluble</json:string><json:string>synergistic effects</json:string><json:string>high concentrations</json:string><json:string>antigen organization</json:string><json:string>cell responsiveness</json:string><json:string>clear differences</json:string><json:string>immunoglobulin synthesis</json:string><json:string>significant proliferative responses</json:string><json:string>cell activators</json:string><json:string>influenza virus</json:string><json:string>influenza viruses</json:string><json:string>cell proliferation</json:string><json:string>superstimulatory function</json:string><json:string>cell subpopulation</json:string><json:string>high amounts</json:string><json:string>molecular strategy</json:string><json:string>activation</json:string><json:string>virus</json:string><json:string>saturating concentrations</json:string><json:string>flow cytometry</json:string><json:string>side scatter parameters</json:string><json:string>culture period</json:string><json:string>saline solution</json:string><json:string>superstimulatory protein</json:string><json:string>soluble antibodies</json:string><json:string>cochin hospital</json:string><json:string>first example</json:string><json:string>cells cells</json:string><json:string>other hand</json:string><json:string>maximal responses</json:string><json:string>suboptimal amounts</json:string><json:string>influenza virus hemagglutinin</json:string><json:string>different forms</json:string><json:string>responder cells</json:string><json:string>different concentrations</json:string><json:string>soluble form</json:string><json:string>triplicate determinations</json:string><json:string>superstimulatory influenza viruses</json:string><json:string>different amounts</json:string><json:string>similar observations</json:string><json:string>adsorption values</json:string><json:string>measurable production</json:string><json:string>independent experiments</json:string><json:string>phosphodiesterase inhibitor pentoxifylline</json:string><json:string>cholera toxin</json:string><json:string>influenza virus glycoprotein hemagglutinin</json:string><json:string>phorbol esters</json:string><json:string>transduction machinery</json:string><json:string>culture medium</json:string><json:string>small amounts</json:string><json:string>obligatory role</json:string><json:string>neonatal mice</json:string><json:string>cell subpopulations</json:string><json:string>respective stimulus</json:string><json:string>high rate</json:string><json:string>transgenic mice</json:string><json:string>inhibitory</json:string></teeft></keywords><author><json:item><name>Ortwin Rott</name><affiliations><json:string>Cochin Hospital, Rene Descartes University, Paris, France</json:string><json:string>*Dr. Rott died at the beginning of this year.</json:string></affiliations></json:item><json:item><name>James J. 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We here report that, if presented in a highly organized form, i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and peritoneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and vice versa. Similarly, anti-Ig-Dex, which on its own cannot incude Ig production in the absence of added cytokines, significantly enhanced Ig synthesis in response to superstimulatory HA. By contrast, poorly organized BCR-ligands (i.e. the same anti- Ig mAb in a soluble form) had either no, or a strong inhibitory effect on virus-triggered lymphocyte activation. Assays with various second messenger-antagonists, however, revealed clear differences in the signaling pathway employed by anti-Ig-Dex and HA, suggesting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. 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Cash, INSERM U.283, Pavillon Hardy A, Cochin Hospital, 27. rue du Fg. Saint-Jacques, 75674 Paris Cedex 14, France.</affiliation></author><idno type="istex">A638AD5133DF017B1457D97864A9A8FBBA70D818</idno><idno type="ark">ark:/67375/6H6-X2L344P7-Q</idno><idno type="DOI">10.1016/S0171-2985(96)80056-8</idno><idno type="PII">S0171-2985(96)80056-8</idno><idno type="article-id">80056</idno></analytic><monogr><title level="j">Immunobiology</title><title level="j" type="abbrev">IMBIO</title><idno type="pISSN">0171-2985</idno><idno type="PII">S0171-2985(96)X8055-0</idno><imprint><publisher>ELSEVIER</publisher><date type="published" when="1996"></date><biblScope unit="volume">196</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="332">332</biblScope><biblScope unit="page" to="349">349</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>1996</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The influenza virus glycoprotein hemagglutinin (HA) behaves as a superstimulatory protein for B lymphocytes from various species. Polyclonal B cell stimulation mediated by HA can be blocked by soluble anti-Ig antibodies. We here report that, if presented in a highly organized form, i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and peritoneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and vice versa. Similarly, anti-Ig-Dex, which on its own cannot incude Ig production in the absence of added cytokines, significantly enhanced Ig synthesis in response to superstimulatory HA. By contrast, poorly organized BCR-ligands (i.e. the same anti- Ig mAb in a soluble form) had either no, or a strong inhibitory effect on virus-triggered lymphocyte activation. Assays with various second messenger-antagonists, however, revealed clear differences in the signaling pathway employed by anti-Ig-Dex and HA, suggesting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. Taken together, these results indicate that the superstimulatory function of influenza virus HA represents a molecular strategy to mimick B cell activation by conventional, highly organized particulate-antigens.</p></abstract></profileDesc><revisionDesc><change when="1996">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-X2L344P7-Q/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Elsevier doc found" wicri:toSee="Elsevier, no converted or simple article"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" </istex:xmlDeclaration><istex:docType PUBLIC="-//ES//DTD journal article DTD version 5.1.0//EN//XML" URI="art510.dtd" name="istex:docType"></istex:docType><istex:document><article version="5.1" xml:lang="en" docsubtype="fla"><item-info><jid>IMBIO</jid><aid>80056</aid><ce:pii>S0171-2985(96)80056-8</ce:pii><ce:doi>10.1016/S0171-2985(96)80056-8</ce:doi><ce:copyright type="other" year="1996">Gustav Fischer Verlag</ce:copyright></item-info><head><ce:title>Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation</ce:title><ce:author-group><ce:author><ce:given-name>Ortwin</ce:given-name><ce:surname>Rott</ce:surname><ce:cross-ref refid="aff1"><ce:sup>1</ce:sup></ce:cross-ref><ce:cross-ref refid="fn1"><ce:sup>*</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>James J.</ce:given-name><ce:surname>Mond</ce:surname><ce:cross-ref refid="aff2"><ce:sup>2</ce:sup></ce:cross-ref></ce:author><ce:author><ce:given-name>Evelyne</ce:given-name><ce:surname>Cash</ce:surname><ce:cross-ref refid="aff1"><ce:sup>1</ce:sup></ce:cross-ref><ce:cross-ref refid="fn2"><ce:sup>a</ce:sup></ce:cross-ref></ce:author><ce:affiliation id="aff1"><ce:label>1</ce:label><ce:textfn>Cochin Hospital, Rene Descartes University, Paris, France</ce:textfn></ce:affiliation><ce:affiliation id="aff2"><ce:label>2</ce:label><ce:textfn>Department of Medicine, Uniformed Services University of the Health Services, Bethesda, Maryland, U.S.A.</ce:textfn></ce:affiliation><ce:footnote id="fn1"><ce:label>*</ce:label><ce:note-para>Dr. Rott died at the beginning of this year.</ce:note-para></ce:footnote><ce:footnote id="fn2"><ce:label>a</ce:label><ce:note-para>Dr. E. Cash, INSERM U.283, Pavillon Hardy A, Cochin Hospital, 27. rue du Fg. Saint-Jacques, 75674 Paris Cedex 14, France.</ce:note-para></ce:footnote></ce:author-group><ce:date-received day="6" month="2" year="1996"></ce:date-received><ce:date-accepted day="6" month="2" year="1996"></ce:date-accepted><ce:abstract id="ab1"><ce:section-title>Abstract</ce:section-title><ce:abstract-sec><ce:simple-para id="SP0005">The influenza virus glycoprotein hemagglutinin (HA) behaves as a superstimulatory protein for B lymphocytes from various species. Polyclonal B cell stimulation mediated by HA can be blocked by soluble anti-Ig antibodies. We here report that, if presented in a highly organized form, i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and peritoneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and <ce:italic>vice versa</ce:italic>. Similarly, anti-Ig-Dex, which on its own cannot incude Ig production in the absence of added cytokines, significantly enhanced Ig synthesis in response to superstimulatory HA. By contrast, poorly organized BCR-ligands (i.e. the same anti- Ig mAb in a soluble form) had either no, or a strong inhibitory effect on virus-triggered lymphocyte activation. Assays with various second messenger-antagonists, however, revealed clear differences in the signaling pathway employed by anti-Ig-Dex and HA, suggesting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. Taken together, these results indicate that the superstimulatory function of influenza virus HA represents a molecular strategy to mimick B cell activation by conventional, highly organized particulate-antigens.</ce:simple-para></ce:abstract-sec></ce:abstract></head><tail><ce:bibliography id="R0005"><ce:section-title>References</ce:section-title><ce:bibliography-sec id="RS0005"><ce:bib-reference id="bib1"><ce:label>1.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>G.J.V.</ce:given-name><ce:surname>Nossal</ce:surname></sb:author><sb:author><ce:given-name>J.W.</ce:given-name><ce:surname>Schrader</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>B lymphocyte-antigen interactions in the initiation of tolerance or immunity</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Transplant. Rev</sb:maintitle></sb:title><sb:volume-nr>23</sb:volume-nr></sb:series><sb:date>1975</sb:date></sb:issue><sb:pages><sb:first-page>138</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib2"><ce:label>2.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Coutinho</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Moller</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Thymus-independent B-cell induction and paralysis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Adv. Immunol</sb:maintitle></sb:title><sb:volume-nr>21</sb:volume-nr></sb:series><sb:date>1975</sb:date></sb:issue><sb:pages><sb:first-page>113</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib3"><ce:label>3.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>D.C.</ce:given-name><ce:surname>Wiley</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Skehel</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Viral membranes</sb:maintitle></sb:title></sb:contribution><sb:host><sb:edited-book><sb:editors><sb:editor><ce:given-name>B.F.</ce:given-name><ce:surname>Fields</ce:surname></sb:editor></sb:editors><sb:book-series><sb:series><sb:title><sb:maintitle>In Virology</sb:maintitle></sb:title><sb:volume-nr>1</sb:volume-nr></sb:series></sb:book-series><sb:date>1990</sb:date><sb:publisher><sb:name>Raven Press</sb:name></sb:publisher></sb:edited-book><sb:pages><sb:first-page>63</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib4"><ce:label>4.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Lees</ce:surname></sb:author><sb:author><ce:given-name>C.M.</ce:given-name><ce:surname>Snapper</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>T cell-independent antigens type 2</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Annu. Rev. Immunol</sb:maintitle></sb:title><sb:volume-nr>13</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>655</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib5"><ce:label>5.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Brunswick</ce:surname></sb:author><sb:author><ce:given-name>F.D.</ce:given-name><ce:surname>Finkelman</ce:surname></sb:author><sb:author><ce:given-name>P.F.</ce:given-name><ce:surname>Highet</ce:surname></sb:author><sb:author><ce:given-name>J.K.</ce:given-name><ce:surname>Inman</ce:surname></sb:author><sb:author><ce:given-name>H.M.</ce:given-name><ce:surname>Dintzis</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Picogram quantities of anti-Ig antibodies coupled to dextran induce B cell proliteration</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>140</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>3364</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib6"><ce:label>6.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Brunswick</ce:surname></sb:author><sb:author><ce:given-name>C.H.</ce:given-name><ce:surname>June</ce:surname></sb:author><sb:author><ce:given-name>F.D.</ce:given-name><ce:surname>Finkelman</ce:surname></sb:author><sb:author><ce:given-name>H.M.</ce:given-name><ce:surname>Dintzis</ce:surname></sb:author><sb:author><ce:given-name>J.K.</ce:given-name><ce:surname>Inman</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Surface immunoglobulin-mediated B-cell activation in the absence of detectable elevations in intracellular ionized calcium: A model for T-cell-independent B-cell activation</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Proc. Natl. Acad. Sci. USA</sb:maintitle></sb:title><sb:volume-nr>86</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>6724</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib7"><ce:label>7.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>G.T.</ce:given-name><ce:surname>Rehe</ce:surname></sb:author><sb:author><ce:given-name>I.M.</ce:given-name><ce:surname>Katona</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Brunswick</ce:surname></sb:author><sb:author><ce:given-name>L.M.</ce:given-name><ce:surname>Wahl</ce:surname></sb:author><sb:author><ce:given-name>C.H.</ce:given-name><ce:surname>June</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Activation of human B lymphocytes by nanogram concentrations of anti-IgM-dextran conjugates</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>20</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>1837</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib8"><ce:label>8.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Brunswick</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Bonvini</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Francis</ce:surname></sb:author><sb:author><ce:given-name>C.C.</ce:given-name><ce:surname>Felder</ce:surname></sb:author><sb:author><ce:given-name>T.</ce:given-name><ce:surname>Hoffman</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Absence of demonstrable phospholipid turnover in B cells stimulated by low mitogenic concentrations of dextran-anti-immunoglobulin conjugates</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>20</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>855</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib9"><ce:label>9.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>E.M.</ce:given-name><ce:surname>Anders</ce:surname></sb:author><sb:author><ce:given-name>A.A.</ce:given-name><ce:surname>Scalzo</ce:surname></sb:author><sb:author><ce:given-name>D.O.</ce:given-name><ce:surname>White</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Influenza viruses are T cell-independent B cell mitogens</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Virol</sb:maintitle></sb:title><sb:volume-nr>50</sb:volume-nr></sb:series><sb:date>1984</sb:date></sb:issue><sb:pages><sb:first-page>960</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib10"><ce:label>10.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>O.</ce:given-name><ce:surname>Rott</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Cash</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Influenza virus hemagglutinin induces differentiation of mature resting B cells and growth arrest of immature WEHI-231 lymphoma cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>152</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>5381</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib11"><ce:label>11.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>O.</ce:given-name><ce:surname>Rott</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Charreire</ce:surname></sb:author><sb:author><ce:given-name>K.</ce:given-name><ce:surname>Mignon-Godefroy</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Cash</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>B cell superstimulatory influenza virus activates peritoneal B cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>155</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>134</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib12"><ce:label>12.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Fazekas</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Rajnavolgyi</ce:surname></sb:author><sb:author><ce:given-name>I.</ce:given-name><ce:surname>Kurucz</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Sintar</ce:surname></sb:author><sb:author><ce:given-name>K.</ce:given-name><ce:surname>Kiss</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Laszlo</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Gergely</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Isolation and characterization of IgG2a-reactive autoantibodies from influenza virusinfected BALB/c-mice</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>20</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>2719</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib13"><ce:label>13.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>L.M.</ce:given-name><ce:surname>Roman</ce:surname></sb:author><sb:author><ce:given-name>L.F.</ce:given-name><ce:surname>Simons</ce:surname></sb:author><sb:author><ce:given-name>R.E.</ce:given-name><ce:surname>Hammer</ce:surname></sb:author><sb:author><ce:given-name>J.F.</ce:given-name><ce:surname>Sambrook</ce:surname></sb:author><sb:author><ce:given-name>M.-J.H.</ce:given-name><ce:surname>Gething</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>The expression of influenza virus hemagglutinin in the pancreatic β cells of transgenic mice results in atuoimmune diabetes</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Cell</sb:maintitle></sb:title><sb:volume-nr>61</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>383</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib14"><ce:label>14.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>O.</ce:given-name><ce:surname>Rott</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Charreire</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Semichon</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Bismuth</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Cash</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>B cell superstimulatory influenza virus (H2-subtype) induces B cell proliferation by a PKC-activating, Ca2+independent mechanism</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>154</sb:volume-nr></sb:series><sb:date>1995</sb:date></sb:issue><sb:pages><sb:first-page>2092</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib15"><ce:label>15.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.H.</ce:given-name><ce:surname>Julius</ce:surname></sb:author><sb:author><ce:given-name>C.H.</ce:given-name><ce:surname>Heusser</ce:surname></sb:author><sb:author><ce:given-name>K.-U.</ce:given-name><ce:surname>Hartmann</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Induction of resting B cells to DNA synthesis by soluble monoclonal anti-immunoglobulin</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>14</sb:volume-nr></sb:series><sb:date>1984</sb:date></sb:issue><sb:pages><sb:first-page>753</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib16"><ce:label>16.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>L.M.T.</ce:given-name><ce:surname>Peçanha</ce:surname></sb:author><sb:author><ce:given-name>C.M.</ce:given-name><ce:surname>Snapper</ce:surname></sb:author><sb:author><ce:given-name>F.D.</ce:given-name><ce:surname>Finkelman</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Dextran-conjugated anti-Ig antibodies as a model for T cell-independent type 2 antigen-mediated stimulation of Ig secretion in vitro. I. Lymphokine dependence</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>146</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>833</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib17"><ce:label>17.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Basten</ce:surname></sb:author><sb:author><ce:given-name>R.</ce:given-name><ce:surname>Brink</ce:surname></sb:author><sb:author><ce:given-name>P.</ce:given-name><ce:surname>Peake</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Adams</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Crosbie</ce:surname></sb:author><sb:author><ce:given-name>S.</ce:given-name><ce:surname>Hartley</ce:surname></sb:author><sb:author><ce:given-name>C.C.</ce:given-name><ce:surname>Goodnow</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Self tolerance in the B-cell repertoire</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Immunol. Rev</sb:maintitle></sb:title><sb:volume-nr>122</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>5</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib18"><ce:label>18.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>D.</ce:given-name><ce:surname>Nemazee</ce:surname></sb:author><sb:author><ce:given-name>D.</ce:given-name><ce:surname>Russell</ce:surname></sb:author><sb:author><ce:given-name>B.</ce:given-name><ce:surname>Arnold</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Haemmerling</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Allison</ce:surname></sb:author><sb:author><ce:given-name>J.F.A.P.</ce:given-name><ce:surname>Miller</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Morahan</ce:surname></sb:author><sb:author><ce:given-name>K.</ce:given-name><ce:surname>Buerki</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Clonal deletion of autospecific B lymphocytes</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Immunol. Rev</sb:maintitle></sb:title><sb:volume-nr>122</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>117</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib19"><ce:label>19.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>C.C.</ce:given-name><ce:surname>Goodnow</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Transgenic mice and analysis of B-cell tolerance</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Annu. Rev. Immunol</sb:maintitle></sb:title><sb:volume-nr>10</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>489</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib20"><ce:label>20.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.F.</ce:given-name><ce:surname>Bachmann</ce:surname></sb:author><sb:author><ce:given-name>U.H.</ce:given-name><ce:surname>Rohrer</ce:surname></sb:author><sb:author><ce:given-name>T.M.</ce:given-name><ce:surname>Kündig</ce:surname></sb:author><sb:author><ce:given-name>K.</ce:given-name><ce:surname>Bürki</ce:surname></sb:author><sb:author><ce:given-name>H.</ce:given-name><ce:surname>Hengartner</ce:surname></sb:author><sb:author><ce:given-name>R.M.</ce:given-name><ce:surname>Zinkernagel</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>The influence of antigen organization on B cell responsiveness</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Science</sb:maintitle></sb:title><sb:volume-nr>262</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>1448</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib21"><ce:label>21.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.P.</ce:given-name><ce:surname>Cooke</ce:surname></sb:author><sb:author><ce:given-name>A.W.</ce:given-name><ce:surname>Heath</ce:surname></sb:author><sb:author><ce:given-name>K.M.</ce:given-name><ce:surname>Shokat</ce:surname></sb:author><sb:author><ce:given-name>Y.</ce:given-name><ce:surname>Zeng</ce:surname></sb:author><sb:author><ce:given-name>F.D.</ce:given-name><ce:surname>Finkelman</ce:surname></sb:author><sb:author><ce:given-name>P.S.</ce:given-name><ce:surname>Linsley</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Howard</ce:surname></sb:author><sb:author><ce:given-name>C.C.</ce:given-name><ce:surname>Goodnow</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Immunoglobulin signal transduction guides the specificity of B cell-T cell interactions and is blocked in tolerant self-reactive B cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Exp. Med</sb:maintitle></sb:title><sb:volume-nr>179</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>425</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib22"><ce:label>22.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>D.G.</ce:given-name><ce:surname>Sieckmann</ce:surname></sb:author><sb:author><ce:given-name>K.</ce:given-name><ce:surname>Holmes</ce:surname></sb:author><sb:author><ce:given-name>P.</ce:given-name><ce:surname>Hornbeck</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Martin</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Guelde</ce:surname></sb:author><sb:author><ce:given-name>S.</ce:given-name><ce:surname>Bondada</ce:surname></sb:author><sb:author><ce:given-name>D.L.</ce:given-name><ce:surname>Longo</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Kenny</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>B cells from M167 pKtransgenic mice fail to proliferate after stimulation with soluble anti-Ig antibodies. A model for antigen-induced B cell anergy</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>152</sb:volume-nr></sb:series><sb:date>1994</sb:date></sb:issue><sb:pages><sb:first-page>4873</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib23"><ce:label>23.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>G.G.B.</ce:given-name><ce:surname>Klaus</ce:surname></sb:author><sb:author><ce:given-name>K.</ce:given-name><ce:surname>Vondy</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Holman</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Selective effects of cholera toxin on the activation of mouse B cells by different polyclonal activators</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>17</sb:volume-nr></sb:series><sb:date>1987</sb:date></sb:issue><sb:pages><sb:first-page>1787</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib24"><ce:label>24.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>N.</ce:given-name><ce:surname>Muthusamy</ce:surname></sb:author><sb:author><ce:given-name>A.R.</ce:given-name><ce:surname>Baluyut</ce:surname></sb:author><sb:author><ce:given-name>B.</ce:given-name><ce:surname>Subbarao</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Differential regulation of surface Ig- and Lyb2 -mediated B cell activation by cyclic AMP. I. Evidence for alternative regulation of signaling through two different receptors linked to phosphatidylinositol hydrolysis in murine B cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>147</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>2483</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib25"><ce:label>25.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>Y.S.</ce:given-name><ce:surname>Li</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Kouassi</ce:surname></sb:author><sb:author><ce:given-name>J.P.</ce:given-name><ce:surname>Revillard</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Cyclic AMP can enhance mouse B cell activation by regulating progression into the late G1/S phase</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>19</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>1721</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib26"><ce:label>26.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Bismuth</ce:surname></sb:author><sb:author><ce:given-name>I.</ce:given-name><ce:surname>Theodorou</ce:surname></sb:author><sb:author><ce:given-name>H.</ce:given-name><ce:surname>Gouy</ce:surname></sb:author><sb:author><ce:given-name>S.</ce:given-name><ce:surname>Le Gouvello</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Bernard</ce:surname></sb:author><sb:author><ce:given-name>P.</ce:given-name><ce:surname>Debré</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Cyclic-AMP-mediated alteration of the CD2 activation process in human T lymphocytes. Preferential inhibition of the phosphoinositide cycle-related transduction pathway</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>18</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>1351</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib27"><ce:label>27.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Lerner</ce:surname></sb:author><sb:author><ce:given-name>B.</ce:given-name><ce:surname>Jacobson</ce:surname></sb:author><sb:author><ce:given-name>R.A.</ce:given-name><ce:surname>Miller</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Cyclic AMP concentrations modulate both calcium flux and hydrolysis of phosphatidylinositol phosphates in mouse T lymphocytes</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>140</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>936</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib28"><ce:label>28.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Liu</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>FK506 and cyclosporin, molecular probes for studying intracellular signal transduction</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Immunol. Today</sb:maintitle></sb:title><sb:volume-nr>14</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>290</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib29"><ce:label>29.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>H.</ce:given-name><ce:surname>Yamada</ce:surname></sb:author><sb:author><ce:given-name>C.H.</ce:given-name><ce:surname>June</ce:surname></sb:author><sb:author><ce:given-name>F.</ce:given-name><ce:surname>Finkelman</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Brunswick</ce:surname></sb:author><sb:author><ce:given-name>M.S.</ce:given-name><ce:surname>Ring</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Lees</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Persistent calcium elevation correlates with the induction of surface immunoglobulin-mediated B cell DNA synthesis</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Exp. Med</sb:maintitle></sb:title><sb:volume-nr>177</sb:volume-nr></sb:series><sb:date>1993</sb:date></sb:issue><sb:pages><sb:first-page>1613</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib30"><ce:label>30.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>A.A.</ce:given-name><ce:surname>Scalzo</ce:surname></sb:author><sb:author><ce:given-name>E.M.</ce:given-name><ce:surname>Anders</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Influenza viruses as lymphocyte mitogens. I. B cell mitogenesis by influenza A viruses of the H2 and H6 subtypes is controlled by the 1-E/C subregion of the major histocompatility complex</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>134</sb:volume-nr></sb:series><sb:date>1985</sb:date></sb:issue><sb:pages><sb:first-page>757</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib31"><ce:label>31.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>K.P.</ce:given-name><ce:surname>Rigley</ce:surname></sb:author><sb:author><ce:given-name>M.M.</ce:given-name><ce:surname>Harnett</ce:surname></sb:author><sb:author><ce:given-name>R.J.</ce:given-name><ce:surname>Phillips</ce:surname></sb:author><sb:author><ce:given-name>G.G.B.</ce:given-name><ce:surname>Klaus</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Analysis of signaling via surface immunoglobulin receptors on B cells from CBA/N mice</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>19</sb:volume-nr></sb:series><sb:date>1989</sb:date></sb:issue><sb:pages><sb:first-page>2081</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib32"><ce:label>32.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>M.L.</ce:given-name><ce:surname>Lindsberg</ce:surname></sb:author><sb:author><ce:given-name>M.</ce:given-name><ce:surname>Brunswick</ce:surname></sb:author><sb:author><ce:given-name>H.</ce:given-name><ce:surname>Yamada</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Lees</ce:surname></sb:author><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Inman</ce:surname></sb:author><sb:author><ce:given-name>C.H.</ce:given-name><ce:surname>June</ce:surname></sb:author><sb:author><ce:given-name>J.J.</ce:given-name><ce:surname>Mond</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Biochemical analysis of the immune B cell defect in xid mice</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>147</sb:volume-nr></sb:series><sb:date>1991</sb:date></sb:issue><sb:pages><sb:first-page>3774</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib33"><ce:label>33.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>Y.</ce:given-name><ce:surname>Nawata</ce:surname></sb:author><sb:author><ce:given-name>A.M.</ce:given-name><ce:surname>Stall</ce:surname></sb:author><sb:author><ce:given-name>L.A.</ce:given-name><ce:surname>Herzenberg</ce:surname></sb:author><sb:author><ce:given-name>E.M.</ce:given-name><ce:surname>Eugui</ce:surname></sb:author><sb:author><ce:given-name>A.C.</ce:given-name><ce:surname>Allison</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Surface immunoglobulin ligands and cytokines differentially affect proliferation and antibody production by human CD5+ and CDS-lymphocytes</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Int. Immunol</sb:maintitle></sb:title><sb:volume-nr>2</sb:volume-nr></sb:series><sb:date>1990</sb:date></sb:issue><sb:pages><sb:first-page>603</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib34"><ce:label>34.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>J.</ce:given-name><ce:surname>Andersson</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Coutinho</ce:surname></sb:author><sb:author><ce:given-name>F.</ce:given-name><ce:surname>Melchers</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Stimulation of murine B lymphocytes to IgG synthesis and secretion by the mitogens lipopolysaccharide and lipoprotein and its inhibition by anti-immunoglobulin antibodies</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>8</sb:volume-nr></sb:series><sb:date>1978</sb:date></sb:issue><sb:pages><sb:first-page>336</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib35"><ce:label>35.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>U.</ce:given-name><ce:surname>Chen-Bettecken</ce:surname></sb:author><sb:author><ce:given-name>E.</ce:given-name><ce:surname>Wecker</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Schimpl</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>IgM RNA switch from membrane to secretary form is prevented by adding antireceptor antibody to bacteriallipopolysaccharide-stimulated murine primary B-cell cultures</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Proc. Natl. Acad. Sci. USA</sb:maintitle></sb:title><sb:volume-nr>82</sb:volume-nr></sb:series><sb:date>1985</sb:date></sb:issue><sb:pages><sb:first-page>7384</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib36"><ce:label>36.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>L.</ce:given-name><ce:surname>Berberich</ce:surname></sb:author><sb:author><ce:given-name>A.</ce:given-name><ce:surname>Schimpl</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Regulation of immunoglobulin gene expression in normal lymphocytes. II. Mechanism of downregulation of immunoglobulin secretion after engagement of the B cell antigen receptor</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Eur. J. Immunol</sb:maintitle></sb:title><sb:volume-nr>22</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>525</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib37"><ce:label>37.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>J.-L.</ce:given-name><ce:surname>Virelizier</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Host defenses against influenza virus: the role of anti-hemagglutinin antibody</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>115</sb:volume-nr></sb:series><sb:date>1975</sb:date></sb:issue><sb:pages><sb:first-page>434</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib38"><ce:label>38.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>R.B.</ce:given-name><ce:surname>Couch</ce:surname></sb:author><sb:author><ce:given-name>J.A.</ce:given-name><ce:surname>Kasel</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Immunity to influenza in man</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Annu. Rev. Microbiol</sb:maintitle></sb:title><sb:volume-nr>37</sb:volume-nr></sb:series><sb:date>1983</sb:date></sb:issue><sb:pages><sb:first-page>529</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib39"><ce:label>39.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>G.L.</ce:given-name><ce:surname>Ada</ce:surname></sb:author><sb:author><ce:given-name>P.D.</ce:given-name><ce:surname>Jones</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>The immune response to influenza infection</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Curro Top. Microbiol. Immunol</sb:maintitle></sb:title><sb:volume-nr>128</sb:volume-nr></sb:series><sb:date>1986</sb:date></sb:issue><sb:pages><sb:first-page>1</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib40"><ce:label>40.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>H.D.</ce:given-name><ce:surname>Klenk</ce:surname></sb:author><sb:author><ce:given-name>R.</ce:given-name><ce:surname>Rott</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>The molecular biology of influenza virus pathogenicity</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>Adv. Virus Res</sb:maintitle></sb:title><sb:volume-nr>34</sb:volume-nr></sb:series><sb:date>1988</sb:date></sb:issue><sb:pages><sb:first-page>247</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference><ce:bib-reference id="bib41"><ce:label>41.</ce:label><sb:reference><sb:contribution><sb:authors><sb:author><ce:given-name>P.A.</ce:given-name><ce:surname>Scherle</ce:surname></sb:author><sb:author><ce:given-name>G.</ce:given-name><ce:surname>Palladino</ce:surname></sb:author><sb:author><ce:given-name>W.</ce:given-name><ce:surname>Gerhard</ce:surname></sb:author></sb:authors><sb:title><sb:maintitle>Mice can recover from pulmonary influenza virus infection in the absence of class I-restricted cytotoxic T cells</sb:maintitle></sb:title></sb:contribution><sb:host><sb:issue><sb:series><sb:title><sb:maintitle>J. Immunol</sb:maintitle></sb:title><sb:volume-nr>148</sb:volume-nr></sb:series><sb:date>1992</sb:date></sb:issue><sb:pages><sb:first-page>212</sb:first-page></sb:pages></sb:host></sb:reference></ce:bib-reference></ce:bibliography-sec></ce:bibliography></tail></article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation</title></titleInfo><titleInfo type="alternative" lang="en" contentType="CDATA"><title>Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation</title></titleInfo><name type="personal"><namePart type="given">Ortwin</namePart><namePart type="family">Rott</namePart><affiliation>Cochin Hospital, Rene Descartes University, Paris, France</affiliation><affiliation>*Dr. Rott died at the beginning of this year.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">James J.</namePart><namePart type="family">Mond</namePart><affiliation>Department of Medicine, Uniformed Services University of the Health Services, Bethesda, Maryland, U.S.A.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Evelyne</namePart><namePart type="family">Cash</namePart><affiliation>Cochin Hospital, Rene Descartes University, Paris, France</affiliation><affiliation>aDr. E. Cash, INSERM U.283, Pavillon Hardy A, Cochin Hospital, 27. rue du Fg. Saint-Jacques, 75674 Paris Cedex 14, France.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="Full-length article" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1996</dateIssued><copyrightDate encoding="w3cdtf">1996</copyrightDate></originInfo><language><languageTerm type="code" authority="iso639-2b">eng</languageTerm><languageTerm type="code" authority="rfc3066">en</languageTerm></language><abstract lang="en">Abstract: The influenza virus glycoprotein hemagglutinin (HA) behaves as a superstimulatory protein for B lymphocytes from various species. Polyclonal B cell stimulation mediated by HA can be blocked by soluble anti-Ig antibodies. We here report that, if presented in a highly organized form, i.e., as anti-Ig mAb coupled to dextran (anti-Ig-Dex), conventional BCR-ligands and influenza viruses act synergistically on murine B cell activation. Proliferative responses of both spellen-derived and peritoneal B cells mediated by suboptimal amounts of HA were significantly augmented by costimulation with anti-Ig-Dex, and vice versa. Similarly, anti-Ig-Dex, which on its own cannot incude Ig production in the absence of added cytokines, significantly enhanced Ig synthesis in response to superstimulatory HA. By contrast, poorly organized BCR-ligands (i.e. the same anti- Ig mAb in a soluble form) had either no, or a strong inhibitory effect on virus-triggered lymphocyte activation. Assays with various second messenger-antagonists, however, revealed clear differences in the signaling pathway employed by anti-Ig-Dex and HA, suggesting that the functional synergy between the two multimeric agents is mediated by engagement of distinct transducing elements. Taken together, these results indicate that the superstimulatory function of influenza virus HA represents a molecular strategy to mimick B cell activation by conventional, highly organized particulate-antigens.</abstract><relatedItem type="host"><titleInfo><title>Immunobiology</title></titleInfo><titleInfo type="abbreviated"><title>IMBIO</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>ELSEVIER</publisher><dateIssued encoding="w3cdtf">1996</dateIssued></originInfo><identifier type="ISSN">0171-2985</identifier><identifier type="PII">S0171-2985(96)X8055-0</identifier><part><date>1996</date><detail type="volume"><number>196</number><caption>vol.</caption></detail><detail type="issue"><number>4</number><caption>no.</caption></detail><extent unit="issue-pages"><start>321</start><end>462</end></extent><extent unit="pages"><start>332</start><end>349</end></extent></part></relatedItem><identifier type="istex">A638AD5133DF017B1457D97864A9A8FBBA70D818</identifier><identifier type="ark">ark:/67375/6H6-X2L344P7-Q</identifier><identifier type="DOI">10.1016/S0171-2985(96)80056-8</identifier><identifier type="PII">S0171-2985(96)80056-8</identifier><identifier type="ArticleID">80056</identifier><accessCondition type="use and reproduction" contentType="copyright">©1996 Gustav Fischer Verlag</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-HKKZVM7B-M">elsevier</recordContentSource><recordOrigin>Gustav Fischer Verlag, ©1996</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/6H6-X2L344P7-Q/record.json</uri></json:item></metadata></istex></record>Pour manipuler ce document sous Unix (Dilib)
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