Donor-derived regulatory B cells are important for suppression of murine sclerodermatous chronic graft-versus-host disease.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Le Huu, D; Matsushita, T; Jin, G; Hamaguchi, Y; Hasegawa, M; Takehara, K; Tedder, TF; Fujimoto, M

Published Date

  • April 18, 2013

Published In

Volume / Issue

  • 121 / 16

Start / End Page

  • 3274 - 3283

PubMed ID

  • 23422748

Pubmed Central ID

  • 23422748

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2012-11-465658

Language

  • eng

Conference Location

  • United States