Mechanistic remodeling and immunoregulatory functions of the B cell-humoral immunity axis in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an immune-mediated disorder characterized by chronic inflammation of the intestinal mucosa, arising from dysregulation across multiple layers of immune control. In recent years, the contribution of B cells and humoral immunity to IBD pathogenesis has gained increasing attention. B cells participate in mucosal immune regulation through differentiation, clonal expansion, and antibody production, and are closely associated with the formation and structural organization of local tertiary lymphoid structures (TLSs). Beyond antigen neutralization, antibodies can modulate inflammatory cell activation and tissue injury via Fc receptor signaling, complement activation, and immune complex-mediated responses. In parallel, intestinal barrier integrity and the extent of antigen exposure critically influence B cell activation and antibody output, forming an interconnected network of local immune processes. Therapeutic strategies targeting the B cell-humoral immunity axis are emerging, including B cell-directed therapies, modulation of antibody effector pathways, and restoration of mucosal immune function. Although accumulating evidence suggests that these approaches may confer benefits in controlling inflammation and modulating immune responses, their efficacy and applicability vary across different strategies and patient populations. In this review, we systematically integrate current evidence on B cell differentiation, local lymphoid organization, and humoral immune responses in IBD. We propose the "B cell-humoral immunity regulatory axis" as a conceptual framework to delineate mucosal immune remodeling in IBD, with the aim of advancing mechanistic understanding and informing the optimization of therapeutic interventions.