B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer

The ability of B cells to negatively regulate cellular immune responses and inflammation has only recently been described. Hallmark papers from a number of distinguished laboratories have identified phenotypically diverse B-cell subsets with regulatory functions during distinct autoimmune diseases, including IL-10-producing B cells, CD5(+) B-1a cells, CD1d(+) marginal zone B cells, and transitional-2-marginal zone precursor B cells. Most recently, a numerically rare and phenotypically unique CD1d(hi)CD5(+)CD19(hi) subset of regulatory B cells has been identified in the spleens of both normal and autoimmune mice. CD1d(hi)CD5(+)B cells with the capacity to produce IL-10 have been named B10 cells as they produce IL-10 exclusively and are the predominant B-cell source of IL-10. Remarkably, B10 cells are potent negative regulators of inflammation and autoimmunity in mouse models of disease in vivo. Herein, our current understanding of B10-cell development and function is reviewed in the context of previous studies that have identified and characterized regulatory B cells, emerging evidence for B10-cell regulation of tumor immunity, and the likelihood that B10 cells exist in humans.