Michael J. Pitcher, Xiaowen Sun, Chiara Dionisi, Lucia Montorsi, S Hermangild Kottoor, Jacqueline H. Y. Siu, Roman Laddach, Rosamond Nuamah, Gavin J. Pettigrew, Richard J. Ellis, Cynthia Bishop, Jahangir Sufi, Pawan Dhami, Heli Vaikkinen, Audrey Kelly, Anna Vossenkämper, Deena L. Gibbons, J P E Spencer
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 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 with healthy GALT. Thus, we identify interactions of strategically located B cells as mediators of immunological equilibrium in human gut.