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 CD1dhiCD5+ 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 CD1dhiCD5+ 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.