B lymphocytes contribute to physiological immunity through organogenesis of secondary lymphoid organs, presentation of antigen to T cells, production of antibodies, and secretion of cytokines. Their role in several autoimmune diseases, mainly as producers of pathogenic antibodies, is also well known. However, certain subsets of B cells are emerging as the important regulatory cell populations in both mouse and human. The regulatory functions of B cells have been demonstrated in a variety of mouse models of autoimmune diseases including collagen-induced arthritis (CIA), experiment autoimmune encephalomyelitis (EAE), anterior chamber-associated immune deviation (ACAID), diabetes, contact hypersensitivity (CHS), and intestinal mucosal inflammation. Accumulating evidence from both mouse and human studies confirms the existence of regulatory B cells, and is beginning to define their mechanisms of action. In this article, we first review the history of B cells with regulatory function in autoimmune diseases, and summarize the current understanding about the characterizations of such B-cell subsets. We then discuss the possible regulatory mechanisms of B cells, and specifically define the role of regulatory B cells in immune homeostasis in the intestine.