Influenza virus hemagglutinin induces differentiation of mature resting B cells and growth arrest of immature WEHI-231 lymphoma cells.
We have investigated the functional requirements for the B cell "mitogenicity" of the influenza virus hemagglutinin (HA). Murine B cell proliferative responses were inducible by either infectious or inactivated virus, and by infected, paraformaldehyde-fixed cells. Viruses of the 12 different HA-subtypes displayed marked differences in their activation potential, classifying them as high (H2, H4, H6, H12), medium (H3, H5, H8, H9), or low (H1, H7, H10, H11) B cell activators. HA-mediated proliferation of resting B cells induced a vigorous Ig synthesis, with a predominance of IgG2b, IgG3, and IgM production. In this activation mode the B cell receptor (BCR) complex seems to be involved because 1) virus-triggered B cell proliferation was blocked by anti-Ig Abs, 2) B cell responses could be competitively inhibited by unfractionated high dose Igs, and 3) addition of BCR-modulating anti-CD45 mAb abrogated subsequent stimulation by HA. Furthermore, 4) influenza viruses were able to induce a growth arrest in the anti-mu sensitive B cell line WEHI-231. Most interestingly, the "tolerogenic" capacity correlated with the B cell stimulatory subtype of the virus, because highly stimulatory HA-subtypes were highly "tolerogenic" whereas low stimulatory subtypes were only marginally effective. Collectively, these observations raise the hypothesis that influenza viruses can cause polyclonal proliferation/differentiation of mature B cells and inactivation/tolerance induction in immature B cells by a mechanism that seems to mimic certain aspects of the physiologic BCR complex-mediated B cell activation.
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INSERM U.283, Cochin Hospital, Paris, France.
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D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000494:pharmacology*; D007136:Immunoglobulins / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008223:Lymphoma / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D014407:Tumor Cells, Cultured; D014759:Viral Envelope Proteins / Q000494:pharmacology*
D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D011947:Receptors, Antigen, B-Cell; D014759:Viral Envelope Proteins; D017493:Leukocyte Common Antigens