Regulatory B cells as inhibitors of immune responses and inflammation

Abstract

Summary: B cells positively regulate immune responses through antibody production and optimal CD4⁺ T‐cell activation. However, a specific and functionally important subset of B cells can also negatively regulate immune responses in mouse autoimmunity and inflammation models. The lack or loss of regulatory B cells has been demonstrated by exacerbated symptoms in experimental autoimmune encephalitis, chronic colitis, contact hypersensitivity, collagen‐induced arthritis, and non‐obese diabetic mouse models. Accumulating evidence suggests that B cells exert their regulatory role through the production of interleukin‐10 (IL‐10) by either B‐1, marginal zone (MZ), or transitional 2–MZ precursor B‐cell subsets. We have recently found that IL‐10‐producing regulatory B cells predominantly localize within a rare CD1d^hiCD5⁺ B‐cell subset that shares cell surface markers with both B‐1 and MZ B cells. We have labeled this specific subset of regulatory B cells as B10 cells to highlight that these rare CD1d^hiCD5⁺ B cells only produce IL‐10 and are responsible for most IL‐10 production by B cells and to distinguish them from other regulatory B‐cell subsets that may also exist. This review focuses on the recent progress in this field and the exciting opportunities for understanding how this unique B‐cell subset influences diverse immune functions.