title: Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease.
abstract: Chronic graft-versus-host disease (cGVHD) is an increasingly frequent cause of morbidity and mortality of allogeneic hematopoietic stem-cell transplantation. Sclerodermatous cGVHD (Scl-cGVHD) is characterized by fibrosis and autoimmune features resembling those of systemic sclerosis (SSc). Transplantation of B10.D2 bone marrow and splenocytes into irradiated BALB/c mice is an established model of human Scl-cGVHD. To examine the role of B cells in Scl-cGVHD, CD19-deficient (CD19(-/-)) mice were used as donors or recipients. CD19(-/-) donors induced more severe Scl-cGVHD than wild-type donors, but use of CD19(-/-) recipients resulted in no significant differences compared with wild-type recipients. Moreover, CD19 deficiency on donor B cells resulted in the expansion of splenic interleukin (IL) -6-producing monocytes/macrophages, cytotoxic CD8(+) T cells, and Th1 cells during the early stage of disease and increased the infiltration of T cells, TGF-β-producing monocytes/macrophages, and Th2 cells into the skin in the later stage of Scl-cGVHD. IL-10-producing regulatory B cells (B10 cells) were not reconstituted by CD19(-/-) donor cells, and early adoptive transfer of B10 cells attenuated the augmented manifestations of CD19(-/-) donor-induced Scl-cGVHD. Therefore, donor-derived B10 cells have a suppressive role in Scl-cGVHD development, warranting future investigation of regulatory B-cell-based therapy for treatment of Scl-cGVHD and SSc.
authors: Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa 920-8641, Japan.
authors: Doanh
authors: D
authors: Le Huu
authors: Takashi
authors: T
authors: Matsushita
authors: Guihua
authors: G
authors: Jin
authors: Yasuhito
authors: Y
authors: Hamaguchi
authors: Minoru
authors: M
authors: Hasegawa
authors: Kazuhiko
authors: K
authors: Takehara
authors: Thomas F
authors: TF
authors: Tedder
authors: Manabu
authors: M
authors: Fujimoto
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology; D055610:Antigens, CD1d / Q000032:analysis / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology*; D039481:CD11b Antigen / Q000032:analysis / Q000276:immunology; D018956:CD5 Antigens / Q000032:analysis / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D005355:Fibrosis / Q000276:immunology / Q000473:pathology; D017353:Gene Deletion; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D055610:Antigens, CD1d; D039481:CD11b Antigen; D018956:CD5 Antigens; D015850:Interleukin-6