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The ensuing immunoglobulin A (IgA) plasma cell response disseminates to regulate bacterial populations and to mediate intestinal immune homeostasis. GALT has roles in the development of the innate-like marginal zone B cell population and is associated with a B cell\u2013mediated contribution to ulcerative colitis (UC) severity and response to therapy. Applying integrated multiomics methodologies, we identified key spatially resolved interactions of B cell subsets including broad regulatory features of double negative 2 (DN2) B cells with potential to maintain homeostasis within microbe-rich mucosa. By contrast, GALT in UC is distorted in composition and spatial distribution of B cell subsets that have altered immunomodulatory potential compared with healthy GALT. 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