Influenza viruses as lymphocyte mitogens. II. Role of I-E molecules in B cell mitogenesis by influenza A viruses of the H2 and H6 subtypes.
Influenza A viruses of the H2 and H6 subtypes behave as T cell-independent B cell mitogens for lymphocytes from strains of mice that express the class II MHC glycoprotein I-E (Ia.7+ haplotypes). We have examined the role of I-E molecules in mitogenesis by these viruses. Lymphocytes from (Ia.7+ X Ia.7-)F1 hybrid strains that express lower levels of I-E antigen than homozygous Ia.7+ strains showed a level of response to H2 and H6 influenza viruses that was intermediate between the high response of the Ia.7+ parent and the low response of the Ia.7- parent. The mitogenic response of H-2k lymphocytes to these viruses was completely inhibited by low concentrations of anti-I-Ek monoclonal antibody that had no effect on B cell proliferation induced by LPS or by influenza A virus of the H3 subtype. Furthermore, incubation of H-2k spleen cells with high concentrations of H2 (but not H3) influenza viruses substantially inhibited the binding of radio-labeled anti-I-Ek, but not anti-I-Ak, monoclonal antibody. Cell mixing experiments indicated that expression of I-E by the B cells was critical to the mitogenic response, whereas I-E expression by accessory cells may not be necessary. The data support a model in which B cell mitogenesis by these viruses results from direct binding of the viruses to I-E molecules on B lymphocytes.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D001667:Binding, Competitive; D006649:Histocompatibility Antigens / Q000032:analysis / Q000276:immunology*; D000949:Histocompatibility Antigens Class II; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D006649:Histocompatibility Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D008934:Mitogens