Document Detail


B cells from patients with chronic GVHD are activated and primed for survival via BAFF-mediated pathways.
MedLine Citation:
PMID:  22896003     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-14
Journal Detail:
Title:  Blood     Volume:  120     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-21     Completed Date:  2012-12-18     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2529-36     Citation Subset:  AIM; IM    
Affiliation:
University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
CA142106/CA/NCI NIH HHS; K08 HL107756/HL/NHLBI NIH HHS; K08 HL113594/HL/NHLBI NIH HHS; K08HL107756/HL/NHLBI NIH HHS; T32 CA009156/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/B-Cell Activating Factor; 0/TNFSF13B protein, human
Comments/Corrections

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