TY - JOUR
T1 - Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD
AU - Khoder, Ahmad
AU - Sarvaria, Anushruti
AU - Alsuliman, Abdullah
AU - Chew, Claude
AU - Sekine, Takuya
AU - Cooper, Nichola
AU - Mielke, Stephan
AU - De Lavallade, Hugues
AU - Muftuoglu, Muharrem
AU - Curbelo, Irina Fernandez
AU - Liu, Enli
AU - Muraro, Paolo A.
AU - Alousi, Amin
AU - Stringaris, Kate
AU - Parmar, Simrit
AU - Shah, Nina
AU - Shaim, Hila
AU - Yvon, Eric
AU - Molldrem, Jeffrey
AU - Rouce, Rayne
AU - Champlin, Richard
AU - McNiece, Ian
AU - Mauri, Claudia
AU - Shpall, Elizabeth J.
AU - Rezvani, Katayoun
N1 - Publisher Copyright:
© 2014 by The American Society of Hematology.
PY - 2014/9/25
Y1 - 2014/9/25
N2 - 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+CD24hiCD38hitransitional B-cell subsets in healthy human donors. Both subsets suppressed the proliferation and interferon-/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.
AB - 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+CD24hiCD38hitransitional B-cell subsets in healthy human donors. Both subsets suppressed the proliferation and interferon-/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.
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U2 - 10.1182/blood-2014-04-571125
DO - 10.1182/blood-2014-04-571125
M3 - Article
C2 - 25051962
AN - SCOPUS:84907272636
SN - 0006-4971
VL - 124
SP - 2034
EP - 2045
JO - Blood
JF - Blood
IS - 13
ER -