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

Publication ,  Journal Article
Kolupaev, OV; Dant, TA; Bommiasamy, H; Bruce, DW; Fowler, KA; Tilley, SL; McKinnon, KP; Sarantopoulos, S; Blazar, BR; Coghill, JM; Serody, JS
Published in: Blood Adv
September 25, 2018

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.

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Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

September 25, 2018

Volume

2

Issue

18

Start / End Page

2307 / 2319

Location

United States

Related Subject Headings

  • T-Lymphocyte Subsets
  • Severity of Illness Index
  • Precursor Cells, B-Lymphoid
  • Osteoblasts
  • Mice, Transgenic
  • Mice
  • Lymphocyte Depletion
  • Immunophenotyping
  • Graft vs Host Disease
  • Gene Expression
 

Citation

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Kolupaev, O. V., Dant, T. A., Bommiasamy, H., Bruce, D. W., Fowler, K. A., Tilley, S. L., … Serody, J. S. (2018). Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans model of cGVHD. Blood Adv, 2(18), 2307–2319. https://doi.org/10.1182/bloodadvances.2017014977
Kolupaev, Oleg V., Trisha A. Dant, Hemamalini Bommiasamy, Danny W. Bruce, Kenneth A. Fowler, Stephen L. Tilley, Karen P. McKinnon, et al. “Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans model of cGVHD.Blood Adv 2, no. 18 (September 25, 2018): 2307–19. https://doi.org/10.1182/bloodadvances.2017014977.
Kolupaev OV, Dant TA, Bommiasamy H, Bruce DW, Fowler KA, Tilley SL, et al. Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans model of cGVHD. Blood Adv. 2018 Sep 25;2(18):2307–19.
Kolupaev, Oleg V., et al. “Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans model of cGVHD.Blood Adv, vol. 2, no. 18, Sept. 2018, pp. 2307–19. Pubmed, doi:10.1182/bloodadvances.2017014977.
Kolupaev OV, Dant TA, Bommiasamy H, Bruce DW, Fowler KA, Tilley SL, McKinnon KP, Sarantopoulos S, Blazar BR, Coghill JM, Serody JS. Impaired bone marrow B-cell development in mice with a bronchiolitis obliterans model of cGVHD. Blood Adv. 2018 Sep 25;2(18):2307–2319.

Published In

Blood Adv

DOI

EISSN

2473-9537

Publication Date

September 25, 2018

Volume

2

Issue

18

Start / End Page

2307 / 2319

Location

United States

Related Subject Headings

  • T-Lymphocyte Subsets
  • Severity of Illness Index
  • Precursor Cells, B-Lymphoid
  • Osteoblasts
  • Mice, Transgenic
  • Mice
  • Lymphocyte Depletion
  • Immunophenotyping
  • Graft vs Host Disease
  • Gene Expression