| Autor: |
Rothstein, Thomas L., Xuemei Zhong, Schram, Brian R., Negm, Robert S., Donohoe, Terrence J., Cabral, Deborah S., Foote, Linda C., Schneider, Thomas J. |
| Předmět: |
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| Zdroj: |
Immunological Reviews; Aug2000, Vol. 176 Issue 1, p116, 18p |
| Abstrakt: |
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 on Fas expression and marked sensitivity of 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-κB 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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