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Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation

Identifieur interne : 001580 ( Istex/Corpus ); précédent : 001579; suivant : 001581

Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation

Auteurs : Ortwin Rott ; James J. Mond ; Evelyne Cash

Source :

RBID : ISTEX:A638AD5133DF017B1457D97864A9A8FBBA70D818

English descriptors

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:A638AD5133DF017B1457D97864A9A8FBBA70D818

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<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>
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<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>
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<title>Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation</title>
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<title>Superstimulatory Influenza Virus and Highly Organized BCR-Ligands Act Synergistically on B Cell Activation</title>
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<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>
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<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>
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<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>
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<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>
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