Professor of Medicine
Medicine, Hematologic Malignancies and Cellular Therapy
School of Medicine
Member of the Duke Cancer Institute
Duke Cancer Institute
School of Medicine
Affiliate of the Duke Regeneration Center
Regeneration Next Initiative
School of Medicine
Sun Yat Sen University (China)
Stanford University, School of Medicine
BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.
Patients with chronic graft-versus-host disease (cGVHD) have increased B cell-activating factor (BAFF) levels, but whether BAFF promotes disease after allogeneic bone marrow transplantation (allo-BMT) remains unknown. In a major histocompatibility complex-mismatched model with cGVHD-like manifestations, we first examined B-lymphopenic μMT allo-BMT recipients and found that increased BAFF levels in cGVHD mice were not merely a reflection of B-cell number. Mice that later developed cGVHD had significantly increased numbers of recipient fibroblastic reticular cells with higher BAFF transcript levels. Increased BAFF production by donor cells also likely contributed to cGVHD, because BAFF transcript in CD4+ T cells from diseased mice and patients was increased. cGVHD manifestations in mice were associated with high BAFF/B-cell ratios and persistence of B-cell receptor (BCR)-activated B cells in peripheral blood and lesional tissue. By employing BAFF transgenic (Tg) mice donor cells, we addressed whether high BAFF contributed to BCR activation in cGVHD. BAFF increased NOTCH2 expression on B cells, augmenting BCR responsiveness to surrogate antigen and NOTCH ligand. BAFF Tg B cells had significantly increased protein levels of the proximal BCR signaling molecule SYK, and high SYK protein was maintained by BAFF after in vitro BCR activation or when alloantigen was present in vivo. Using T cell-depleted (BM only) BAFF Tg donors, we found that BAFF promoted cGVHD manifestations, circulating GL7+ B cells, and alloantibody production. We demonstrate that pathologic production of BAFF promotes an altered B-cell compartment and augments BCR responsiveness. Our findings compel studies of therapeutic targeting of BAFF and BCR pathways in patients with cGVHD.
Jia, Wei, et al. “BAFF promotes heightened BCR responsiveness and manifestations of chronic GVHD after allogeneic stem cell transplantation.” Blood, vol. 137, no. 18, May 2021, pp. 2544–57. Pubmed, doi:10.1182/blood.2020008040.
An Ear-Tissue Model for High-Resolution In Vivo Imaging.
Jiao, Y; Zhang, P; DeOliveira, D; Drago, N; Chao, NJ; Chen, BJ
Jiao, Yiqun, et al. “An Ear-Tissue Model for High-Resolution In Vivo Imaging.” Blood, vol. 116, no. 21, AMER SOC HEMATOLOGY, 2010, pp. 623–623.
Allogeneic Committed Hematopoietic Progenitors Are Protective Against Radiation.
<jats:title>Abstract</jats:title> <jats:p>Whole-body irradiation may lead to bone marrow failure and death. It was previously reported that congenic myeloerythroid-restricted progenitors are able to radioprotect lethally irradiated animals. However, this approach will not be practical because syngeneic/congenic donors are rarely available in humans. To solve this problem, we investigated whether allogeneic committed progenitors are also radioprotective. Hematopoietic committed progenitors were isolated by FACS based on the presence of early progenitor marker CD244 and the absence of stem cell marker CD150 (CD244+CD150−). BALB/c mice (H2d) were lethally irradiated with 8.5 Gy. Within 4 hours of irradiation, the irradiated mice were infused with 5x105 sorted hematopoietic progenitors from major histocompatibility complex mistmatched C57BL/6 donors (H2b). As shown in the Figure B, all the mice in the radiation control group died within 15 days post irradiation (median survival time: 13 days). Infusion of hematopoietic committed progenitors significantly prolonged the survival of the lethally irradiated mice (P=0.0018, median survival time: 28 days). These results are similar to the results obtained from congenic hematopoietic progenitors using 1x105 cells (Figure A, P<0.0001, median survival time: 10 days vs. 28 days). These data suggest that allogeneic hematopoietic committed progenitor cells are also able to mediate radioprotective effects. Similar to the congenic hematopoietic committed progenitors, allogeneic progenitors may also exert radioprotective effects by jumpstarting hematologic recovery post irradiation. These cells may be stockpiled and used as “off-the-shelf” products for radiation injury and other applications.</jats:p> <jats:p>Figure Figure</jats:p>
Chen, BJ; Deoliveira, D; Chao, NJ
Chen, Benny J., et al. “Allogeneic Committed Hematopoietic Progenitors Are Protective Against Radiation.” Blood, vol. 110, no. 11, American Society of Hematology, 2007, pp. 4871–4871. Crossref, doi:10.1182/blood.v110.11.4871.4871.
Hematopoiteic stem cell doses correlate with the speed of immune reconstitution after allogeneic stem cell transplantation.
Chen, BJ; Cui, XY; Chao, NJ
Chen, B. J., et al. “Hematopoiteic stem cell doses correlate with the speed of immune reconstitution after allogeneic stem cell transplantation.” Blood, vol. 96, no. 11, AMER SOC HEMATOLOGY, 2000, pp. 772A-772A.
Non-GVHD-inducing CD62L− memory T cells promote new T cell regeneration from hematopoietic stem cells
Chen, BJ; Cui, X; Son, J; Chao, NJ
Chen, B. J., et al. “Non-GVHD-inducing CD62L− memory T cells promote new T cell regeneration from hematopoietic stem cells.” Biology of Blood and Marrow Transplantation, vol. 10, Elsevier BV, 2004, pp. 23–23. Crossref, doi:10.1016/j.bbmt.2003.12.093.
Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation
Anti-Inflammatory Agents, Non-Steroidal
Antineoplastic Agents, Alkylating
Blood Cell Count
Bone Marrow Cells
Bone Marrow Purging
Bone Marrow Transplantation
Colony-Forming Units Assay
Disease Models, Animal
Drugs, Chinese Herbal
Graft vs Host Disease
Graft vs Leukemia Effect
Graft vs Tumor Effect
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Radiation Injuries, Experimental
Receptor, Angiotensin, Type 1
Receptors, Antigen, T-Cell
Recovery of Function
Reproducibility of Results
Specific Pathogen-Free Organisms
Stem Cell Transplantation
Toll-Like Receptor 4
Tumor Cells, Cultured
Professor of Medicine
Box 103866 Med Ctr, Durham, NC 27710
GSRB1 Rm 4004B, 905 S Lasalle Street, Durham, NC 27710