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 11 (MHC 11) 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 11 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 11 or CD40, and is restricted exclusively to virus-specific B cells.