title: IL-10+ regulatory B cells are enriched in cord blood and may protect against cGVHD after cord blood transplantation.
abstract: Cord blood (CB) offers a number of advantages over other sources of hematopoietic stem cells, including a lower rate of chronic graft-versus-host disease (cGVHD) in the presence of increased HLA disparity. Recent research in experimental models of autoimmunity and in patients with autoimmune or alloimmune disorders has identified a functional group of interleukin-10 (IL-10)-producing regulatory B cells (Bregs) that negatively regulate T-cell immune responses. At present, however, there is no consensus on the phenotypic signature of Bregs, and their prevalence and functional characteristics in CB remain unclear. Here, we demonstrate that CB contains an abundance of B cells with immunoregulatory function. Bregs were identified in both the naive and transitional B-cell compartments and suppressed T-cell proliferation and effector function through IL-10 production as well as cell-to-cell contact involving CTLA-4. We further show that the suppressive capacity of CB-derived Bregs can be potentiated through CD40L signaling, suggesting that inflammatory environments may induce their function. Finally, there was robust recovery of IL-10-producing Bregs in patients after CB transplantation, to higher frequencies and absolute numbers than seen in the peripheral blood of healthy donors or in patients before transplant. The reconstituting Bregs showed strong in vitro suppressive activity against allogeneic CD4(+) T cells, but were deficient in patients with cGVHD. Together, these findings identify a rich source of Bregs and suggest a protective role for CB-derived Bregs against cGVHD development in CB recipients. This advance could propel the development of Breg-based strategies to prevent or ameliorate this posttransplant complication.
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Anushruti
authors.initials: A
authors.lastname: Sarvaria
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Rafet
authors.initials: R
authors.lastname: Basar
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Rohtesh S
authors.initials: RS
authors.lastname: Mehta
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Hila
authors.initials: H
authors.lastname: Shaim
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Muharrem
authors.initials: M
authors.lastname: Muftuoglu
authors.affiliation: Department of Haematology, Imperial College London, London, United Kingdom.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Khoder
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Takuye
authors.initials: T
authors.lastname: Sekine
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Elif
authors.initials: E
authors.lastname: Gokdemir
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Kayo
authors.initials: K
authors.lastname: Kondo
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: David
authors.initials: D
authors.lastname: Marin
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: May
authors.initials: M
authors.lastname: Daher
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Amin M
authors.initials: AM
authors.lastname: Alousi
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Alsuliman
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Enli
authors.initials: E
authors.lastname: Liu
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Betul
authors.initials: B
authors.lastname: Oran
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Amanda
authors.initials: A
authors.lastname: Olson
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Roy B
authors.initials: RB
authors.lastname: Jones
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Uday
authors.initials: U
authors.lastname: Popat
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Chitra
authors.initials: C
authors.lastname: Hosing
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Richard
authors.initials: R
authors.lastname: Champlin
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Stem Cell Transplantation and Cellular Therapy, University of Texas MD Anderson Cancer Center, Houston, TX; and.
authors.forename: Katayoun
authors.initials: K
authors.lastname: Rezvani
mesh_terms: D000328:Adult; D000368:Aged; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction; D055815:Young Adult
chemical_list: C508609:IL10 protein, human; D016753:Interleukin-10