B cells in inflammatory bowel disease

Inflammatory bowel diseases (IBD) have traditionally been considered T cell-driven disorders; however, accumulating evidence challenges this view and underscores a critical, multifaceted role for B cells in the pathogenesis of chronic intestinal inflammation. In the healthy gut, B cells contribute to immune tolerance and mucosal protection primarily through the production of secretory IgA and the regulation of the microbiota. During IBD, the B cell compartment is markedly altered, characterized by increased infiltration of IgA and IgG-secreting PCs, altered humoral responses against gut microbiota and self-antigens, the formation of tertiary lymphoid structures and the emergence of pro-inflammatory subsets such as interferon-induced Sca1⁺PD-L1⁺ B cells. Experimental models have demonstrated both pathogenic and regulatory roles for B cells, which may explain the limited efficacy of pan-B cell depleting therapies, such as rituximab, in clinical settings. This review highlights the evolving landscape of B cell biology in IBD, emphasizing the need for selective therapeutic approaches that distinguish between protective and pathogenic B cells. A deeper understanding of the spatial, phenotypic, and temporal dynamics of intestinal B cell subsets may facilitate the development of precise immunotherapies in IBD.