Fcµ Receptor Promotes the Survival and Activation of Marginal Zone B Cells and Protects Mice against Bacterial Sepsis

Jun Liu, Hanying Zhu, Jiawen Qian, Ermeng Xiong, Lumin Zhang, Yan-Qing Wang, Yiwei Chu, Hiromi Kubagawa, Takeshi Tsubata, Ji-Yang Wang

The marginal zone B cells (MZB) are located at the interface between the circulation and lymphoid tissue and as a gatekeeper play important roles in both innate and adaptive immune responses. We have previously found that MZB are significantly reduced in mice deficient in the IgM Fc receptor (FcμR) but how FcμR regulates the development and function of MZB remains unknown. In this study, we found that both marginal zone precursor (MZP) and MZB were decreased inFcμR-/-mice. The reduction of MZP and MZB was not due to impaired proliferation of these cells but rather due to their increased death. Further analysis revealed thatFcμR-/-MZB had reduced tonic BCR signal, as evidenced by their decreased levels of phosphorylated SYK and AKT relative to WT MZB. MZB inFcμR-/-mice responded poorly to LPSin vivowhen compared with MZB in WT mice. Consistent with the reduced proportion of MZB and their impaired response to LPS, antibody production against the type 1 T-independent Ag, NP-LPS, was significantly reduced inFcμR-/-mice. Moreover,FcμR-/-mice were highly susceptible toCitrobacter rodentium-induced sepsis. These results reveal a critical role for FcμR in the survival and activation of MZB and in protection against acute bacterial infection.