No abstract

Follicular dendritic cells (FDC) are specialized antigen-presenting cells to cognate B cells in the follicle of the lymphoid tissues. FDC also support survival and proliferation of the B cells, leading to the germinal center formation. FDC therefore play a central role in humoral immune responses. However, molecular and functional characteristics of FDC are largely unknown, because it is difficult to isolate and analyze FDC due to a very small number of FDC in the lymphoid tissues and the fragility by mechanical and chemical stresses in vitro. In this report, we established a novel method for FDC isolation from the spleen of naïve mice by flow cytometry and analyzed the phenotypical and functional characteristics. The isolated FDC, which accounted for ~0.2% of the spleen cells of naïve mice, were CD45(-), FDC-M2(+), and ICAM-1(+), and supported the survival and LPS-induced proliferation of B cells. We also showed that a neutralizing antibody against B cell activating factor TNF family (BAFF) suppressed FDC-dependent B cell proliferation in the presence of LPS, but not survival, demonstrating the evidence that FDC-derived BAFF is involved in B cell proliferation.

Antibody exerts various immune responses via binding to Fc receptors expressed on immune cells. Although several reports have demonstrated that IgM prevents autoantibody production, the role of IgM Fc receptors is largely unknown. To analyze the involvement of Fcα/μR (CD351), an Fc receptor for IgM and IgA expressed on B cells and follicular dendritic cells (FDCs), in IgM-mediated suppression of autoantibody production, we generated mice deficient in Fcα/μR on the background of MRL/MpJ-Fas(lpr/lpr) (Fcamr(-/-)Fas(lpr/lpr)) mice. Fcamr(-/-)Fas(lpr/lpr) mice showed significantly lower titers of IgG autoantibodies against double strand (ds) DNA, histone and cardiolipin in the sera than did Fcamr(+/+)Fas(lpr/lpr) mice. Moreover, Fcamr(-/-)Fas(lpr/lpr) mice showed higher survival rate at the ages of 28, 32 and 40 weeks old, compared with Fcamr(+/+)Fas(lpr/lpr) mice. These results suggest that Fcα/μR enhances, rather than suppresses, autoantibody production.