The Dual Roles of Regulatory B Cells in Infection, Cancer, and Immunity

ABSTRACT Regulatory B cells (Bregs) are a functionally defined yet phenotypically heterogeneous subset of lymphocytes that are essential for maintaining immune homeostasis. Their canonical function is regulated through the secretion of interleukin‐10 (IL‐10), a potent anti‐inflammatory cytokine. However, accumulating evidence indicates that other molecules, such as IL‐35 and transforming growth factor‐β, and that of contact‐dependent pathways, such as Programmed Cell Death Ligand‐1 (PD‐L1) and Programmed Cell Death‐1 (PD‐1), also play indispensable roles in their regulatory arsenal. This review examines the immunoregulatory roles of Bregs across diverse clinical contexts, including infectious diseases, cancers, autoimmune disorders (such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and uveitis), and organ transplantation. Crucially, we highlight a fundamental functional dichotomy: although Bregs confer protection against autoimmunity and promote transplant tolerance, they concurrently drive the progression of chronic infections and malignancies by dampening antipathogen and antitumor immune responses. This functional dichotomy highlights the complexity of immune regulation, where Bregs act as critical nodes balancing health and pathology. The immense therapeutic potential by modulating Bregs activity and unresolved questions that will guide the future frontiers of Bregs research are essentially discussed.