Atlas of human gut-associated lymphoid tissue reveals immunomodulatory interactions of B cells

Gut-associated lymphoid tissue (GALT) is organized lymphoid tissue that responds chronically to antigens, including whole bacteria, sampled from the gut lumen. 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 also associated with a B cell–mediated 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 to healthy GALT. Thus, we identify interactions of strategically located B cells as mediators of immunological equilibrium in human gut.