Inducible resistance to Fas-mediated apoptosis in B cells  

作　　者：ROTHSTEIN THOMAS L Departments of Medicine and Microbiology, and the Evans Memorial Department of Clinical Research, Boston University Medical Center, Boston, MA, USA 

出　　处：《Cell Research》2000年第4期245-266,共22页细胞研究（英文版）

摘　　要：Apoptosis produced in B cells through Fas (APO-1, CD95) triggering is regulated by signals derived from other surface receptors: CD40 engagement produces upregulation of Fas expres. sion and marked susceptibility to Fas-induced cell death, whereas antigen receptor engagement, or IL-4R engagement, inhibits Fas killing and in so doing induces a state of Fas-resistance, even in otherwise sensitive, CD40-stimulated targets. Surfaceim. munoglobulin and IL-4R utilize at least partially distinct pathways to produce Fas-resistance that differentially depend on PKC and STAT6, respectively. Further, surface immunoglob- "lin signaling for inducible Fas-resistance bypasses Bib, requires NF-GB, and entails new macromolecular synthesis. Terminal effectors of B cell Fas-resistance include the known anti-apoptotic gene products, Bcl-xL and FLIP, and a novel anti-apoptotic gene that encodes FAIM (Fas Apoptosis Inhibitory Molecule). faim was identified by differential display and exists in two alternatively spliced forms; maim-S is broadly expressed, but faim-L expression is tissue-specific. The FAIM sequence is highly evolu tionarily conserved, suggesting an important role for this molecule throughout phylogeny. Inducible resistance to Fas killing is hypothesized to protect foreign antigen-specific B cells during potentially hazardous interactions with FasL-bearing T cells, whereas autoreactive B cells fail to become Fas-resistant and are deleted via Fas-dependent cytotoxicity. Inadvertent or aberrant acquisition of Fas-resistance may permit autoreactive B cells to escape Fas deletion, and malignant lymphocytes to impede anti-tumor immunity.

关 键 词：Apoptosis Fas B lymphocytes FAIM FLIP BCL-XL surface immunoglobulin IL-4R CD40 AUTOREACTIVITY 

分 类 号：Q25[生物学—细胞生物学]