%0 Journal Article
%T Antigen receptor signaling and cell death resistance controls intestinal humoral response zonation.
%A Raso F
%A Liu S
%A Simpson MJ
%A Barton GM
%A Mayer CT
%A Acharya M
%A Muppidi JR
%A Marshak-Rothstein A
%A Reboldi A
%J Immunity
%V 56
%N 10
%D 2023 10 10
%M 37714151
%F 43.474
%R 10.1016/j.immuni.2023.08.018
%X Immunoglobulin A (IgA) maintains commensal communities in the intestine while preventing dysbiosis. IgA generated against intestinal microbes assures the simultaneous binding to multiple, diverse commensal-derived antigens. However, the exact mechanisms by which B cells mount broadly reactive IgA to the gut microbiome remains elusive. Here, we have shown that IgA B cell receptor (BCR) is required for B cell fitness during the germinal center (GC) reaction in Peyer's patches (PPs) and for generation of gut-homing plasma cells (PCs). We demonstrate that IgA BCR drove heightened intracellular signaling in mouse and human B cells, and as a consequence, IgA+ B cells received stronger positive selection cues. Mechanistically, IgA BCR signaling offset Fas-mediated death, possibly rescuing low-affinity B cells to promote a broad humoral response to commensals. Our findings reveal an additional mechanism linking BCR signaling, B cell fate, and antibody production location, which have implications for how intestinal antigen recognition shapes humoral immunity.