Regulatory B cells in skin and connective tissue diseases.

While B cells are generally considered to be positive regulators of humoral immune responses due to their ability to differentiate into plasmablasts/plasma cells and produce antibodies, B cells also modulate immune responses through antigen presentation and cytokine secretion. Moreover, "regulatory B cells" that suppress immune responses have been recognized as an important new component of the immune system. In mice, the function of regulatory B cells is almost exclusively dependent on IL-10. The cell-surface phenotype of murine IL-10-producing regulatory B cells is reported to be CD1d(hi)CD5(+) or CD1d(hi)CD21(hi)CD23(+)IgM(hi), and thus their phenotype overlaps with that of CD5(+) B-1a cells, CD1d(hi)CD21(hi)CD23(lo)IgM(hi) marginal zone (MZ) B cells, and CD1d(hi)CD21(hi)CD23(hi)IgM(hi) T2-MZ precursor B cells. Contrary to earlier work that suggested a minor role for B cells in contact hypersensitivity, regulatory B cells are now known to have a critical inhibitory functions in this type of immune response. Furthermore, studies using murine disease models have demonstrated that regulatory B cells play a significant role in autoimmune connective tissue diseases such as rheumatoid arthritis and systemic lupus erythematosus, as well as organ-specific autoimmune diseases including experimental autoimmune encephalomyelitis and inflammatory bowel disease. In comparison to mouse regulatory B cells, little is known regarding their human counterparts. One recent study demonstrates that human CD19(+)CD24(hi)CD38(hi) B cells possess regulatory capacity. Clarifying the molecular mechanisms by which regulatory B cells suppress immune responses will be of great benefit in the development of new B cell-targeted therapeutic strategies.