Signaling via LTβR on the lamina propria stromal cells of the gut is required for IgA production

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Abstract
Peyer's patches (PPs) and/or mesenteric lymph nodes (MLNs) are thought to be essential for immunoglobulin A (IgA) production. We found that the severe IgA deficiency in lymphotoxin-deficient (LT−/−) mice could be fully reversed by reconstitution with LT-expressing bone marrow, despite the absence of both LNs and PPs. The number of IgA precursors from LT−/− mice was not reduced, and they were able to migrate into the lamina propria (LP) of wild-type mice but not of LTβR−/− mice. Consistently, lymphoid tissue chemokines and adhesion molecules were reduced within the LP of LTα−/− and LTβR−/− mice. IgA deficiency in LTα−/− mice was reversed by the transplantation of a segment of RAG-1 (recombination-activating gene 1)–deficient intestine, which confirmed the dispensability of the MLNs and PPs and the sufficiency of the LT-mediated gut microenvironment for IgA production.