Key Points• Human IgM memory B cells possess immunoregulatory properties analogous to transitional B cells.• IL-10-producing B cells are deficient in cGVHD.A subset of regulatory B cells (Bregs) in mice negatively regulate T-cell immune responses through the secretion of regulatory cytokines such as IL-10 and direct cell-cell contact and have been linked to experimental models of autoimmunity, inflammation, and cancer. However, the regulatory function of Bregs in human disease is much less clear.Here we demonstrate that B cells with immunoregulatory properties are enriched within both the CD19 1 IgM 1 CD27 1 memory and CD19 1 CD24 hi CD38 hi transitional B-cell subsets in healthy human donors. Both subsets suppressed the proliferation and interferon-g production of CD3/CD28-stimulated autologous CD4 1 T cells in a dose-dependent manner, and both relied on IL-10 secretion as well as cell-cell contact, likely mediated through CD80 and CD86, to support their full suppressive function. Moreover, after allogeneic stem cell transplantation, Bregs from patients with chronic graft-versus-host disease (cGVHD) were less frequent and less likely to produce IL-10 than were Bregs from healthy donors and patients without cGVHD. These findings suggest that Bregs may be involved in the pathogenesis of cGVHD and support future investigation of regulatory B cell-based therapy in the treatment of this disease. (Blood. 2014;124(13):2034-2045

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