Appendiceal B lymphocytes contribute to the pathogenesis of experimental colitis through fueling colonic CD4+ T polarization

Abstract

The appendix, a component of the gut-associated lymphoid tissue enriched with B lymphocytes, plays a pivotal role in intestinal mucosal immunity. Previous studies have indicated that prior appendectomy may prevent the onset of ulcerative colitis (UC); however, its therapeutic role in UC remains unclear, and prophylactic appendectomy is not a realistic approach to prevent UC. In this study, we confirmed that appendectomy alleviates dextran sodium sulphate (DSS)-induced chronic murine colitis and further demonstrated that appendiceal B (APB) lymphocytes exacerbate colonic inflammation by migrating to the colon via the CCL20–CCR6 axis and facilitating colonic CD4⁺ T cell-mediated T helper 1 (Th1) and T helper 17 (Th17) immune responses. Single-cell sequencing of colonic tissues revealed IgG⁺ B cell-skewed responses in patients with UC, and APB cell expansion was positively correlated with disease severity. Immunofluorescence co-staining suggested that colonic B cells of UC patients related to the appendix. These findings highlight the therapeutic potential of appendectomy and B cell-targeted immunotherapy in UC treatment and further introduce the hypothesis that UC with appendiceal orifice inflammation may represent a distinct subtype of the disease.