FCRL5 promotes T cell-independent innate-like B cell responses and counter-regulates tolerance through the Lyn/SHP-1 circuit (IRM8P.717)

• DOI: 10.4049/jimmunol.192.supp.127.18
• Publication Date: 2023-01-01T09:26:26Z
• Authors: Eugene Becker; Zilu Zhu; Woong-Jai Won; Riccardo Dalla-Fa...; Randall Davis
• Keywords: LYN; Innate lymphoid cell

Abstract The earliest phases of humoral defense are orchestrated by splenic marginal zone (MZ) and body cavity-derived B1 B cells. These frontline responders have been termed “innate-like” given their broadly-reactive natural antibody repertoires capacity for rapid responses to T cell-independent (TI) antigens. Despite key contributions primary responses, why these cells possess such prompt responsivity innate-stimulation is poorly understood. discovery a family Fc receptor-like (FCRL) molecules with homology the classical FCRs IgG IgE, complex tyrosine-based function, preferential cell expression has introduced new level regulation. Although in vivo functions not yet investigated, human FCRL (hFCRL) members becoming increasingly appreciated associations immune-related diseases. In particular, hFCRL3 emerged as generalized risk factor autoimmunity. To better understand role cells, we investigated its closest relative mouse FCRL5 (mFCRL5). This molecule shares homologous extracellular domains, binary signaling, innate-like expression. Here demonstrate that Fcrl5 deficiency impairs TI antigens differentially modulates autoimmunity lupus-prone SHP-1 Lyn mutant mice. data indicate critical mFCRL5 regulating function at interface host tolerance.