APOPTOSIS IN L929 CELLS EXPRESSING A CD40 FAS CHIMERIC RECEPTOR - DISSOCIATION OF STIMULATORY FROM INHIBITORY DEATH SIGNALING FUNCTIONS/

A chimeric transmembrane receptor was constructed by fusing the extrac ellular domain of human CD40 to the transmembrane/intracellular domain of human Fas. When stably overexpressed in L929, the chimera retained the ligand binding specificity of CD40 and the basic signalling prope rties of Fas since an apoptotic response could be induced in a dose-de pendent manner upon administration of recombinant, soluble CD40 ligand trimer or immobilized antiCD40 antibodies. However, this apoptotic re sponse was independent of actinomycin D which is in contrast to result s previously reported for L929 cells stably expressing wildtype human Fas. A labile protein factor was postulated to be responsible for inhi bition of Fas-induced apoptosis in these cells. The apoptotic Fas sign al tranduced by the chimeric CD40/Fas receptor is not regulated by thi s putative inhibitor. Our data suggest that the extracellular domains of CD40 and Fas form functionally similar mono- and multimeric structu res and that the extracellular domain of Fas participates in the regul ation of Fas-specific signal transduction. (C) 1994 Academic Press, In c.