mTORC1-independent IgA production: a unique pathway for gut immune homeostasis

The mammalian target of rapamycin (mTOR) complex 1 (mTORC1) regulates various cellular processes, including immune responses. Previous studies have demonstrated that mTORC1 plays a crucial role in B cell differentiation and the production of IgM and IgG antibodies in response to foreign antigens. However, its role in steady-state antibody production remains poorly understood. In this study, we found that RaptorB-/- mice, which have a B cell-specific deletion of Raptor (an essential component of mTORC1), retained gut-associated IgA production. Conversely, IgM and IgG subclasses were virtually absent due to the loss of peripheral IgM+ mature B cells. We also found that IgA-producing cells were driven by the gut microbiota and were primarily localized in the intestinal lamina propria of RaptorB-/- mice. Consistently, IgA produced in RaptorB-/- mice was functional in its ability to bind gut bacteria and contributed to maintaining gut microbiota α-diversity, although its repertoire was restricted compared with that of control mice. Our findings demonstrated a distinct population of IgA-producing cells that develop independently of mTORC1 and contribute to gut homeostasis, thereby distinguishing them from conventional IgM- and IgG-producing cells.