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.