Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans model of cGVHD.

Published

Journal Article

Chronic graft-versus-host disease (cGVHD) causes significant morbidity and mortality in patients after allogeneic bone marrow (BM) or stem cell transplantation (allo-SCT). Recent work has indicated that both T and B lymphocytes play an important role in the pathophysiology of cGVHD. Previously, our group showed a critical role for the germinal center response in the function of B cells using a bronchiolitis obliterans (BO) model of cGVHD. Here, we demonstrated for the first time that cGVHD is associated with severe defects in the generation of BM B lymphoid and uncommitted common lymphoid progenitor cells. We found an increase in the number of donor CD4+ T cells in the BM of mice with cGVHD that was negatively correlated with B-cell development and the frequency of osteoblasts and Prrx-1-expressing perivascular stromal cells, which are present in the B-cell niche. Use of anti-DR3 monoclonal antibodies to enhance the number of donor regulatory T cells (Tregs) in the donor T-cell inoculum ameliorated the pathology associated with BO in this model. This correlated with an increased number of endosteal osteoblastic cells and significantly improved the generation of B-cell precursors in the BM after allo-SCT. Our work indicates that donor Tregs play a critical role in preserving the generation of B-cell precursors in the BM after allo-SCT. Approaches to enhance the number and/or function of donor Tregs that do not enhance conventional T-cell activity may be important to decrease the incidence and severity of cGVHD in part through normal B-cell lymphopoiesis.

Full Text

Duke Authors

Cited Authors

  • Kolupaev, OV; Dant, TA; Bommiasamy, H; Bruce, DW; Fowler, KA; Tilley, SL; McKinnon, KP; Sarantopoulos, S; Blazar, BR; Coghill, JM; Serody, JS

Published Date

  • September 25, 2018

Published In

  • Blood Adv

Volume / Issue

  • 2 / 18

Start / End Page

  • 2307 - 2319

PubMed ID

  • 30228128

Pubmed Central ID

  • 30228128

Electronic International Standard Serial Number (EISSN)

  • 2473-9537

Digital Object Identifier (DOI)

  • 10.1182/bloodadvances.2017014977

Language

  • eng

Conference Location

  • United States