| B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways. | |
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MedLine Citation:
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PMID: 22896003 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD). Patients with cGVHD have delayed B-cell reconstitution and elevated BAFF to B-cell ratios compared to patients without cGVHD. The mechanisms promoting and sustaining B-cell activation in this disease, however, remain unknown. As BAFF increases murine B-cell metabolism and survival and maintains autoreactive B-cell clones, we performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than 1 year from the time of allogeneic hematopoietic stem cell transplantation. We found that B cells from patients with active cGVHD were in a heightened metabolic state and were resistant to apoptosis. Exogenous BAFF treatment amplified cell size and survival in B cells from these patients. We found significantly increased signaling through ERK and AKT that associated with decreased levels of proapoptotic Bim, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. Thus, we identify a role for BAFF in the pathogenesis of cGVHD and define B-cell activation and survival pathways suitable for novel therapeutic development in cGVHD. |
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Authors:
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Jessica L Allen; Matthew S Fore; Jenna Wooten; Philip A Roehrs; Nazmim S Bhuiya; Todd Hoffert; Andrew Sharf; Allison M Deal; Paul Armistead; James Coghill; Don A Gabriel; Robert Irons; Amber Essenmacher; Thomas C Shea; Kristy Richards; Corey Cutler; Jerome Ritz; Jonathan Serody; Albert S Baldwin; Stefanie Sarantopoulos |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-08-14 |
Journal Detail:
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Title: Blood Volume: 120 ISSN: 1528-0020 ISO Abbreviation: Blood Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-09-21 Completed Date: 2012-12-18 Revised Date: 2013-05-02 |
Medline Journal Info:
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Nlm Unique ID: 7603509 Medline TA: Blood Country: United States |
Other Details:
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Languages: eng Pagination: 2529-36 Citation Subset: AIM; IM |
Affiliation:
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University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Apoptosis* B-Cell Activating Factor / immunology, metabolism* B-Lymphocytes / immunology*, metabolism, pathology Cell Size Cells, Cultured Chronic Disease Female Flow Cytometry Follow-Up Studies Graft vs Host Disease / etiology*, pathology, therapy Hematologic Neoplasms / complications*, pathology, therapy Hematopoietic Stem Cell Transplantation / adverse effects* Humans Immunoblotting Lymphocyte Activation Male Middle Aged Signal Transduction* Transplantation, Homologous Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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CA142106/CA/NCI NIH HHS; K08 HL107756/HL/NHLBI NIH HHS; K08 HL113594/HL/NHLBI NIH HHS; K08HL107756/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/B-Cell Activating Factor; 0/TNFSF13B protein, human |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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