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Immune tolerance to both self-antigens and innocuous non–self-antigens is essential to protect the host against chronic inflammatory diseases and tissue damage. A wide range of cell types and suppressive molecules are involved in induction and maintenance of tolerance. In addition to their key function in the production of immunoglobulins, B cells can regulate immune responses through their surface molecules and secretion of cytokines. Regulatory B (Breg) cells are characterized by their immunosuppressive capacity, which is often mediated through IL-10 secretion. However, IL-35 and TGF-β have also been associated with B cell–mediated immunosuppression. Several types of murine and human Breg cells have been described, such as mouse CD5⁺CD1d^hi B10 cells, CD21^hiCD23^hiCD24^hi transitional stage 2–like B cells, and CD138⁺ plasma cells and plasmablasts. Human Breg cell types include CD27 …