Effects of FcμR expression on B cells activation

Abstract

Abstract FcμR is present on the cell surface of B cells as well as other antigen presenting cells where they bind the secreted form of IgM (sIgM). Our previous studies have shown that follicular B cells internalize sIgM continuously in vivo and that lack of sIgM or the FcμR on B cells results in diminished IgG responses following influenza virus infection. We aim to determine the mechanisms underlying the need for sIgM in the development of IgG responses. For this we generated HELB-FcmR−/− and HELB-FcmR+/+ mice. In vitro stimulation of purified B cells from these mice with HEL-OVA conjugate in the presence of OVA-specific OTII CD4 T cells showed an antigen-dose-dependent stimulation of both types of B cells. However, FcmR−/− B cells proliferated less at intermediate and low doses of antigen compared to controls, while they proliferated similar as wild type B cells following high-dose antigen stimulation. Intravenous injection of CD45.1-expressing C57BL/6 mice with B cells from either FcmR-deficient or -sufficient CD45.2+ HELB mice together with sheep red blood cells conjugated to HEL showed no significant differences in HEL-specific serum IgM or IgG, or frequencies of HEL-specific B cells between mice receiving either type of B cell, as assessed by ELISA and FACS, respectively. Ongoing studies are aimed at determining whether antigen-dose affects the need for FcmR expression in vivo. For that we have created mixed bone marrow (BM) irradiation chimeras with 2% BM from CD45.2 HELB or HELB-FcmR−/− mice, and 98% CD45.1 wild type BM. To-date our studies suggest that FcmR-IgM interaction enhances B cell proliferation when antigen is limiting. Future studies are aimed at testing this conclusion and explore how sIgM-FcmR interaction enhanced B cell responses.