title: Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD.
abstract: 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.
authors: Department of Haematology, Imperial College London, Hammersmith Campus, London, United Kingdom;
authors: Ahmad
authors: A
authors: Khoder
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Anushruti
authors: A
authors: Sarvaria
authors: Department of Haematology, Imperial College London, Hammersmith Campus, London, United Kingdom;
authors: Abdullah
authors: A
authors: Alsuliman
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Claude
authors: C
authors: Chew
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Takuya
authors: T
authors: Sekine
authors: Department of Haematology, Imperial College London, Hammersmith Campus, London, United Kingdom;
authors: Nichola
authors: N
authors: Cooper
authors: University of Wuerzburg, Wuerzburg, Germany;
authors: Stephan
authors: S
authors: Mielke
authors: Department of Haematology, Imperial College London, Hammersmith Campus, London, United Kingdom;
authors: Hugues
authors: H
authors: de Lavallade
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Muharrem
authors: M
authors: Muftuoglu
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Irina
authors: I
authors: Fernandez Curbelo
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Enli
authors: E
authors: Liu
authors: Division of Brain Sciences, Imperial College London, United Kingdom;
authors: Paolo A
authors: PA
authors: Muraro
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Amin
authors: A
authors: Alousi
authors: Department of Haematology, Imperial College London, Hammersmith Campus, London, United Kingdom;
authors: Kate
authors: K
authors: Stringaris
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Simrit
authors: S
authors: Parmar
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Nina
authors: N
authors: Shah
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Hila
authors: H
authors: Shaim
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Eric
authors: E
authors: Yvon
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Jeffrey
authors: J
authors: Molldrem
authors: Baylor College of Medicine. Houston, TX; and.
authors: Rayne
authors: R
authors: Rouce
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Richard
authors: R
authors: Champlin
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Ian
authors: I
authors: McNiece
authors: University College, London, United Kingdom.
authors: Claudia
authors: C
authors: Mauri
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Elizabeth J
authors: EJ
authors: Shpall
authors: Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Centre, Houston, TX;
authors: Katayoun
authors: K
authors: Rezvani
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism; D018941:Antigens, CD19 / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D051927:CD24 Antigen / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002450:Cell Communication; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D006086:Graft vs Host Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007156:Immunologic Memory; D056747:Immunomodulation; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
chemical_list: D018941:Antigens, CD19; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D051927:CD24 Antigen; D016207:Cytokines; D007075:Immunoglobulin M; D018836:Inflammation Mediators; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D016753:Interleukin-10; D051997:ADP-ribosyl Cyclase 1