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

Blood. 2014 Sep 25;124(13):2034-45. doi: 10.1182/blood-2014-04-571125. Epub 2014 Jul 22.


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(+)IgM(+)CD27(+) memory and CD19(+)CD24(hi)CD38(hi) transitional B-cell subsets in healthy human donors. Both subsets suppressed the proliferation and interferon-γ production of CD3/CD28-stimulated autologous CD4(+) 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Antigens, CD19 / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • CD24 Antigen / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Case-Control Studies
  • Cell Communication
  • Cells, Cultured
  • Chronic Disease
  • Cytokines / biosynthesis
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / metabolism
  • Humans
  • Immunoglobulin M / immunology*
  • Immunologic Memory*
  • Immunomodulation
  • Immunophenotyping
  • Inflammation Mediators / metabolism
  • Interleukin-10 / biosynthesis
  • Lymphocyte Activation / immunology
  • Lymphocyte Count
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7


  • Antigens, CD19
  • B7-1 Antigen
  • B7-2 Antigen
  • CD24 Antigen
  • Cytokines
  • Immunoglobulin M
  • Inflammation Mediators
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Interleukin-10
  • ADP-ribosyl Cyclase 1