Objective <p>Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder characterized by dysregulated intestinal immune responses. Accumulating evidence indicates that B-lineage cells play important roles in shaping mucosal immunity. This review aims to summarize the physiological and pathological roles of intestinal B-lineage cells in IBD, with a particular focus on their functional remodeling during biologic therapy and emerging strategies to overcome biologic resistance.</p> Methods <p>Relevant literature on B-lineage cells, IBD, mucosal immunity, and biologic therapies was searched and reviewed.</p> Results <p>Under physiological conditions, plasmablasts and plasma cells maintain intestinal homeostasis through IgA secretion, whereas B lymphocytes contribute via cytokine production, antigen presentation, and cellular interactions that support epithelial repair and barrier integrity. In IBD, B-lineage cells undergo pathogenic remodeling, with expanded effector subsets exhibiting enhanced inflammatory cytokine production, altered antibody profiles, and increased interactions with T cells, myeloid cells, and stromal cells. These changes disrupt epithelial integrity and sustain maladaptive immune activation, contributing to chronic mucosal inflammation. Biologic therapies targeting TNF, α4β7 integrin, and IL-12/23 exert direct and indirect effects on B-lineage cells, modulating their trafficking, survival, and functional states, and partially restoring immune balance. Nevertheless, persistent cellular plasticity and dysregulated survival signaling may enable pathogenic B-lineage subsets to retain inflammatory potential, contributing to treatment non-response or secondary loss of efficacy.</p> Conclusion <p>B-lineage cells play critical roles in both intestinal homeostasis and IBD pathogenesis. Understanding their functional remodeling during biologic therapy may provide insights into treatment resistance and inform emerging strategies to overcome biologic resistance in IBD.</p>