Bregs

Regulatory B cells, or Bregs, are a heterogeneous subset of B lymphocytes that regulate immune responses and promote tolerance. Their regulatory activity is mainly mediated by the secretion of anti-inflammatory cytokines, especially interleukin-10 (IL-10), but can also involve transforming growth factor beta (TGF-β) and interleukin-35, as well as cell-contact–dependent mechanisms.

Phenotypes: In humans, no single universal Breg marker exists. IL-10–producing B cells have been described across several phenotypes, including CD19+CD24hiCD38hi transitional B cells, CD19+CD24hiCD27+ memory B cells, and CD19+CD1dhiCD5+ B cells. In mice, CD19+CD1dhiCD5+ B cells are frequently cited as a regulatory subset; IL-10 production is a defining function rather than a fixed phenotype. Other regulatory B-cell populations express PD-L1 or secrete IL-35, contributing to their suppressive capacity.

Functions: Bregs can suppress effector T cell proliferation and cytokine production (notably Th1 and Th17 responses), promote regulatory T cells, and modulate antigen-presenting cells such as dendritic cells and macrophages. They act through cytokines and through cell-surface molecules such as PD-L1, CD80, and CD86 to inhibit activation and promote tolerance.

Clinical relevance: Altered Breg numbers or function have been reported in autoimmune diseases (for example multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus), infections, cancer, and transplantation contexts. Some therapies aim to boost Breg activity to restore tolerance, while others seek to balance Breg and proinflammatory B cell populations. Research remains challenged by Breg heterogeneity and the lack of universal markers.