Enhanced Humoral Immune Responses Against T-Independent Antigens In Fc Alpha/Mu R-Deficient Mice

IgM is an antibody class common to all vertebrates that plays a primary role in host defenses against infection. Binding of IgM with an antigen initiates the complement cascade, accelerating cellular and humoral immune responses. However, the functional role of the Fc receptor for IgM in such immune responses remains obscure. Here we show that mice deficient in Fc alpha/mu R, an Fc receptor for IgM expressed on B cells and follicular dendritic cells (FDCs), have enhanced germinal center formation and affinity maturation and memory induction of IgG3(+) B cells after immunization with T-independent (TI) antigens. Moreover, Fc alpha/mu R-deficient mice show prolonged antigen retention by marginal zone B (MZB) cells and FDCs. In vitro studies demonstrate that interaction of the IgM immune complex with Fc alpha/mu R partly suppress TI antigen retention by MZB cells. We further show that downregulation of complement receptor (CR) 1 and CR2 or complement deprivation by in vivo injection with anti-CR1/2 antibody or cobra venom factor attenuates antigen retention by MZB cells and germinal center formation after immunization with TI antigens in Fc alpha/mu R-/- mice. Taken together, these results suggest that Fc alpha/mu R negatively regulates TI antigen retention by MZB cells and FDCs, leading to suppression of humoral immune responses against T-independent antigens.