| B cell receptor triggering sensitizes human B cells to TRAIL-induced apoptosis. | |
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MedLine Citation:
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PMID: 20709941 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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TRAIL is known to cause death in tumor cells, but physiological regulation of its activity remains poorly characterized. We demonstrate that BCR triggering sensitizes transformed centroblast-like BL cells and peripheral blood memory B cells to TRAIL-mediated apoptosis. The sensitization correlated with surface down-regulation and intracellular retention of TRAIL-R4, along with changes in the expression of several Bcl-2 protein family members. Although enhancing FAS-mediated cell death, CD40 activation protected B cells from TRAIL-induced apoptosis. Combination of Ig cross-linking with CD40 ligation did not prevent TRAIL-R4 down-regulation but induced changes in the mitochondria-regulated pathway of apoptosis that are known to be associated with resistance to TRAIL. Human CD5(+) B cells, presumably stimulated by reactivity to self without immunological help, exhibited very high ex vivo sensitivity to TRAIL. Our results define the first B-lymphocyte-specific physiological signal that increases cellular sensitivity to TRAIL. This may be important for our understanding of TRAIL involvement in the control of B cell responses and aid in designing TRAIL-based therapies for B cell lymphomas. |
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Authors:
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Andre Ortlieb Guerreiro-Cacais; Jelena Levitskaya; Victor Levitsky |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-13 |
Journal Detail:
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Title: Journal of leukocyte biology Volume: 88 ISSN: 1938-3673 ISO Abbreviation: J. Leukoc. Biol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-02 Completed Date: 2010-11-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8405628 Medline TA: J Leukoc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 937-45 Citation Subset: IM |
Affiliation:
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Johns Hopkins University School of Medicine, 733 North Broadway, Baltimore, MD 21205, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibody Specificity Antigens, CD40 / immunology, physiology Apoptosis / genetics, physiology Apoptosis Regulatory Proteins / genetics B-Lymphocyte Subsets / cytology, immunology B-Lymphocytes / cytology*, immunology* Cell Culture Techniques Cell Line Down-Regulation Flow Cytometry Gene Expression Regulation Humans Immunologic Memory Receptors, Antigen, B-Cell / genetics*, physiology TNF-Related Apoptosis-Inducing Ligand / genetics, physiology* Tumor Necrosis Factor-alpha / genetics bcl-X Protein / genetics |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD40; 0/Apoptosis Regulatory Proteins; 0/Receptors, Antigen, B-Cell; 0/TNF-Related Apoptosis-Inducing Ligand; 0/Tumor Necrosis Factor-alpha; 0/bcl-X Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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