Resistance of murine B-lymphoma cell lines to Fas-mediated apoptosis

Murine B-lymphoma cell lines have served as useful model systems for studying B-cell receptor (BCR)-mediated signal transduction in B cells at various stages of development. Cross-linking of the IgM BCR on several B-lymphoma cell lines can result in apoptosis. Ligation of CD95 (Fas) on splenic B cells can also induce apoptosis. Interestingly, cross-linking of the BCR can protect splenic B cells from Fas-mediated killing. In order to examine the effects of signals from the Fas receptor, a panel of B-lymphoma cell lines expressing different levels of the Fas receptor were initially tested for sensitivity to an anti-Fas monoclonal antibody and a Fas ligand-bearing cell line. Expression of the Fas receptor on the B-lymphoma cell lines did not correlate with their capacity to undergo Fas-induced apoptosis. Of the three sensitive cell lines, only the A20.2J cell line was protected from Fas-mediated killing via cross-linking of the BCR. Additionally, two of three resistant cell lines became sensitive to Fas-induced apoptosis upon treatment with soluble CD40L or with the protein synthesis inhibitor cyclohexamide. These studies provide a system for analyzing why certain B-lymphoma cell lines are resistant to Fas-induced apoptosis and for how signals are integrated from Fas and BCR in the determination of cell fate.