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

Identifieur interne : 000284 ( France/Analysis ); précédent : 000283; suivant : 000285

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

Auteurs : Ortwin Rott [France] ; James J. Mond [États-Unis] ; Evelyne Cash [France]

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


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ISTEX:A638AD5133DF017B1457D97864A9A8FBBA70D818

Le document en format XML

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<term>Adsorption values</term>
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<term>Cell activation</term>
<term>Cell activators</term>
<term>Cell encounter</term>
<term>Cell proliferation</term>
<term>Cell proliferative responses</term>
<term>Cell responses</term>
<term>Cell responsiveness</term>
<term>Cell stimulation</term>
<term>Cell subpopulation</term>
<term>Cell subpopulations</term>
<term>Cells cells</term>
<term>Cholera toxin</term>
<term>Clear differences</term>
<term>Cochin hospital</term>
<term>Culture medium</term>
<term>Culture period</term>
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<term>Different concentrations</term>
<term>Different forms</term>
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<term>High amounts</term>
<term>High concentrations</term>
<term>High rate</term>
<term>Immunoglobulin</term>
<term>Immunoglobulin synthesis</term>
<term>Immunol</term>
<term>Independent experiments</term>
<term>Influenza</term>
<term>Influenza virus</term>
<term>Influenza virus glycoprotein hemagglutinin</term>
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<term>Influenza viruses</term>
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<term>Inhibitory effects</term>
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<term>Lymphocyte activation</term>
<term>Maximal responses</term>
<term>Measurable production</term>
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<term>Neonatal mice</term>
<term>Obligatory role</term>
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<term>Pathway</term>
<term>Phorbol esters</term>
<term>Phosphodiesterase inhibitor pentoxifylline</term>
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<term>Proliferative responses</term>
<term>Reagent</term>
<term>Receptor</term>
<term>Respective stimulus</term>
<term>Responder cells</term>
<term>Rott</term>
<term>Saline solution</term>
<term>Saturating concentrations</term>
<term>Side scatter parameters</term>
<term>Significant proliferative responses</term>
<term>Similar observations</term>
<term>Small amounts</term>
<term>Soluble</term>
<term>Soluble antibodies</term>
<term>Soluble form</term>
<term>Suboptimal amounts</term>
<term>Subtype virus</term>
<term>Superstimulatory</term>
<term>Superstimulatory function</term>
<term>Superstimulatory influenza virus</term>
<term>Superstimulatory influenza viruses</term>
<term>Superstimulatory protein</term>
<term>Synergistic effects</term>
<term>Transduction</term>
<term>Transduction machinery</term>
<term>Transgenic mice</term>
<term>Triplicate determinations</term>
<term>Virus</term>
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<div type="abstract" xml: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.</div>
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