An early CD4+ T cell-dependent immunoglobulin A response to influenza infection in the absence of key cognate T-B interactions.
Contact-mediated interactions between CD4+ T cells and B cells are considered crucial for T cell-dependent B cell responses. To investigate the ability of activated CD4+ T cells to drive in vivo B cell responses in the absence of key cognate T-B interactions, we constructed radiation bone marrow chimeras in which CD4+ T cells would be activated by wild-type (WT) dendritic cells, but would interact with B cells that lacked expression of either major histocompatibility complex class II (MHC II) or CD40. B cell responses were assessed after influenza virus infection of the respiratory tract, which elicits a vigorous, CD4+ T cell-dependent antibody response in WT mice. The influenza-specific antibody response was strongly reduced in MHC II knockout and CD40 knockout mice. MHC II-deficient and CD40-deficient B cells in the chimera environment also produced little virus-specific immunoglobulin (Ig)M and IgG, but generated a strong virus-specific IgA response with virus-neutralizing activity. The IgA response was entirely influenza specific, in contrast to the IgG2a response, which had a substantial nonvirus-specific component. Our study demonstrates a CD4+ T cell-dependent, antiviral IgA response that is generated in the absence of B cell signaling via MHC II or CD40, and is restricted exclusively to virus-specific B cells.
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens / Q000502:physiology; D002450:Cell Communication; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology*
D000914:Antibodies, Viral; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007070:Immunoglobulin A; D007074:Immunoglobulin G