Influenza A virus hemagglutinin is a B cell-superstimulatory lectin.
Influenza A viruses display T cell-independent polyclonal B cell-activating properties which are mediated by the B cell-superstimulatory envelope glycoprotein hemagglutinin (HA). In this report, the receptor-binding requirements for B cell activation by influenza viruses were expected. Neuraminidase treatment of resting mature B cells from BALB/c mice abrogated late (proliferation/immunoglobulin synthesis), early (up-regulation of cell surface markers, including CD25, B220, and B7-1) and very-early events (homotypic adhesion) in virus-responding B lymphocytes. Similarly, pretreatment of murine responder cells with different inhibitors of N-glycosylation (tunicamycin, deoxymannojirimycin) significantly suppressed subsequent B lymphocyte activation by HA, but not control responses to lipopolysaccharide or anti-mu. Assays with chimeric HA transfectants, expressing the loop region of epitope B (amino acids 155-160) of the globular head of H2 (high B cell-stimulatory subtype) or H3 (medium-stimulatory subtype) on the protein backbone of a low-stimulatory subtype (H1) failed to alter the B cell-stimulatory activity of the virus, suggesting that the hypervariable loop region is not crucial in determining the B cell-activating properties of the protein. Collectively, our results imply that the B cell-superstimulatory function of influenza virus HA is not mediated by a direct protein/protein interaction, but via binding of HA to terminal sialic acid residues on cell surface receptor glycoproteins. These findings identify the influenza virus HA glycoprotein as the first viral lectin with lymphocyte-activating properties.
Rott
O
O
INSERM U. 283, Hôpital Cochin, Université René Descartes, Paris, France.
Charreire
J
J
Cash
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E
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015415:Biomarkers; D002449:Cell Aggregation / Q000187:drug effects; D002478:Cells, Cultured; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology* / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis; D009980:Influenza A virus / Q000276:immunology*; D037102:Lectins / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000494:pharmacology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018089:Superantigens / Q000276:immunology* / Q000378:metabolism
D015415:Biomarkers; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007136:Immunoglobulins; D037102:Lectins; D011956:Receptors, Cell Surface; D018089:Superantigens; D009439:Neuraminidase