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

Blood Advances
Oleg V KolupaevJonathan S Serody

Abstract

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...Continue Reading

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Citations

Dec 27, 2018·British Journal of Haematology·Xiaoping LiXi Zhang
Mar 16, 2021·Frontiers in Immunology·Chao HongXiaoming Gao
Jun 9, 2021·The Journal of Clinical Investigation·Gérard SociéBruce R Blazar
Sep 25, 2021·Bone Marrow Transplantation·Teresa Lopes RamosJosé A Pérez-Simón
Aug 10, 2021·Blood·Ronjon Chakraverty, Takanori Teshima

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