Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD

Abstract

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

CD24hiCD27+ and plasmablast-like regulatory B cells in human chronic graft-versus-host disease

“…In line with Khoder et al, 24 we found significantly lower Bregs in BLOOD, 12 MARCH 2015 x VOLUME 125, NUMBER 11…”

“…The results in the 11 patients with cGVHD in this same study also suggested that IL-10-producing B cells were less frequent in cGVHD patients than in healthy controls and AHSCT recipients without cGVHD. 24 Although we detected a significant concentration of Bregs in the CD27 1 B-cell compartment, we could not replicate the findings of specific enrichment either in the transitional or in the CD5 1 B-cell compartment as previously described. 55,56 Several factors may explain these discrepancies.…”

“…1 Depending on the disease, the phenotypic markers and in vitro stimulation used, different B-cell subsets are enriched in Bregs, including CD24 hi CD27 1 B cells 7 and CD24 hi CD38 hi transitional B cells. 21,24 GC reactions may play a major role in the pathogenesis of cGVHD in mice. [25][26][27] GC-derived "plasmablast-like" B cells are increased in human cGVHD.…”

The correlation of CD19 + CD24 + CD38 + B cells and other clinicopathological variables with the proportion of circulating Tregs in breast cancer patients

“…CD19 ?-CD24 hi CD38 hi cells play a key role in inflammation process and autoimmune diseases; however, the role of CD19 ? CD24 hi CD38 hi cells in the development of human cancer is less studied [28]. In this study, first we focused on breast cancer and examined the percentage of T and B regulatory cells and compared them with healthy individuals.…”

Regulatory B cells promote graft-versus-host disease prevention and maintain graft-versus-leukemia activity following allogeneic bone marrow transplantation

“…In addition, the quantity and quality impairment of Bregs was also observed in human chronic GVHD. 20,21 However, it remains unclear whether Bregs could alleviate acute GVHD while maintaining graft-versus-leukemia (GVL) effects. Here, we show that the immunosuppressive potential of Bregs can be used to suppress acute GVHD without compromising the effects of GVL activity based on results from a mouse model and a clinical cohort study.…”