ERP117014 PRJEB34152 ena-STUDY-WASHINGTON UNIVERSITY SCHOOL OF MEDICINE-26-08-2019-20:18:53:792-295 Secretory IgA enhances GI tract B cells priming and systemic IgG responses against commensal bacteria Immunoglobulin (Ig)A, the primary antibody produced at mucosal surfaces, is believed to inhibit adaptive immune responses against commensal bacteria in the gastrointestinal tract. Here, we utilized an in vitro system to expand and screen IgA memory B cells (MBCs) for recognition of gut bacteria in the context of secretory IgA (sIgA) deficiency in polymeric Ig receptor (Pigr–/–) mice. Contrary to the prevailing hypothesis that IgA prevents bacterial entry and immune priming, sIgA-deficient mice showed decreased anti-bacterial IgA specificities as assessed using flow cytometry. IgA B cell responses against certain taxa such as those of order Bacteriodales showed greater dependence on sIgA. Notably, sIgA also facilitated the generation of anti-bacterial IgG B cells, which provided increased resistance to intraperitoneal infection by commensal bacteria. Together, these data suggest that sIgA primes the gut immune system towards commensal bacteria to increase anti-bacterial IgA and IgG responses, enhance immunity, and prevent sepsis. Immunoglobulin (Ig)A, the primary antibody produced at mucosal surfaces, is believed to inhibit adaptive immune responses against commensal bacteria in the gastrointestinal tract. Here, we utilized an in vitro system to expand and screen IgA memory B cells (MBCs) for recognition of gut bacteria in the context of secretory IgA (sIgA) deficiency in polymeric Ig receptor (Pigr–/–) mice. Contrary to the prevailing hypothesis that IgA prevents bacterial entry and immune priming, sIgA-deficient mice showed decreased anti-bacterial IgA specificities as assessed using flow cytometry. IgA B cell responses against certain taxa such as those of order Bacteriodales showed greater dependence on sIgA. Notably, sIgA also facilitated the generation of anti-bacterial IgG B cells, which provided increased resistance to intraperitoneal infection by commensal bacteria. Together, these data suggest that sIgA primes the gut immune system towards commensal bacteria to increase anti-bacterial IgA and IgG responses, enhance immunity, and prevent sepsis. ENA-FIRST-PUBLIC 2019-10-26 ENA-LAST-UPDATE 2019-08-26