Receptor-specific regulation of B-cell susceptibility to Fas-mediated apoptosis and a novel Fas apoptosis inhibitory molecule
| Autor: | D. S. Cabral, Xuemei Zhong, Linda C. Foote, Robert S. Negm, Brian R. Schram, Terrence J. Donohoe, Thomas L. Rothstein, Thomas J. Schneider |
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| Rok vydání: | 2000 |
| Předmět: |
Molecular Sequence Data
Immunology Apoptosis Receptors Cell Surface Fas ligand Downregulation and upregulation Immune Tolerance medicine Animals Humans Immunology and Allergy Amino Acid Sequence fas Receptor B cell B-Lymphocytes CD40 Sequence Homology Amino Acid biology Proteins Fas receptor Molecular biology medicine.anatomical_structure biology.protein STAT protein Signal transduction Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Immunological Reviews. 176:116-133 |
| ISSN: | 0105-2896 |
| DOI: | 10.1034/j.1600-065x.2000.00616.x |
| Popis: | The susceptibility of primary B cells to Fas (APO-1, CD95)-mediated apoptosis is modulated by signals derived from additional surface receptors: CD40 engagement produces upregulation of Fas expression and marked sensitivity to Fas-induced cell death, whereas antigen receptor engagement, or interleukin-4 receptor (IL-4R) engagement, inhibits Fas killing and thereby produces Fas resistance, even in otherwise susceptible, CD40-stimulated targets. Surface immunoglobulin (sIg) and IL-4R utilize distinct signaling pathways to produce Fas resistance that rely on protein kinase C and signal transducer and activator of transcription 6, respectively sIg signaling for inducible Fas resistance requires nuclear factor-kappaB and depends on new macromolecular synthesis. Proximate mediators for Fas resistance include the known anti-apoptotic gene products Bcl-xL and FLIP (but not Btk), and a novel anti-apoptotic gene that encodes Fas apoptosis inhibitory molecule (FAIM). FAIM was identified by differential display and was cloned as two alternatively spliced forms: FAIM-S is broadly expressed, whereas faim-L expression is tissue specific. faim is highly evolutionarily conserved, suggesting an important function throughout phylogeny. Inducible resistance to Fas-mediated apoptosis is speculated to protect antigen-specific B cells during potentially dangerous interactions with FasL-bearing T cells; the elevated sIg-signaling threshold for inducible Fas resistance in autoreactive, tolerant B cells would insure against autoimmunity. However, aberrant acquisition of Fas resistance may allow autoreactive B cells to escape Fas deletion and malignant lymphocytes to thwart antitumor immunity. |
| Databáze: | OpenAIRE |
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