Molecular base of the defenses against infection by IgM and IgA

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IgM plays pivotal role in innate immunity by initiating classical complement cascade. Recently, an novel Fc receptor for IgM and IgA, Fcα/μR, was finaly cloned, but its involvement in IgM-mediated immunity was unclear. Here, we show that marginal zone B (MZB) cells and follicular dendritic cells (FDC) preferentially express Fcα/μR. In Fcα/μR-deficient mice, although GC formation against TD antigen was normal, that against TI antigen was enhanced, in which both B cells and FDC were involved. Formation of antigen-IgM complex decreased BCR-mediated activation and complement dependent antigen deposition of B cells via IgM-Fcα/μR interaction. Fcα/μR-deficient mice showed enhanced antigen retention by MZB cells and FDC, and CXCL13 expression in lymphoid organ in response to TI antigen. Moreover, TI antigen induced GC formation in Fcα/μR-deficient mice result in the affinity maturation of IgG3. Abrogation of complement pathway completely attenuated these phenotypes. Collectively, Fcα/μR may exert fine-tuning mechanism of IgM-mediated immune responses against TI antigens by interacting with the complement cascades.