APO-1 (CD95)-dependent and -independent antigen receptor-induced apoptosis in human T and B cell lines.

Certain B and T cell lines respond to activation signals, e.g. through the antigen receptor, by undergoing apoptotic cell death. In T cells it has been recently shown that TCR-mediated apoptosis involves APO-1/Fas(CD95) receptor-ligand interaction. To investigate whether the TCR-CD3 complex can trigger alternative apoptosis pathways we generated subclones of the T cell line Jurkat which were completely resistant towards APO-1-mediated apoptosis. These JurkatR cells differed phenotypically from sensitive parental JurkatS cells only by the lack of APO-1 protein expression. Although JurkatR cells responded normally to anti-CD3 stimulation by expression of APO-1 ligand they failed to undergo anti-CD3-induced apoptosis. Thus, in Jurkat cells APO-1-mediated apoptosis was the main, and might be the only, mechanism for anti-CD3-induced cell death. However, BL-60 B cells, highly sensitive to anti-IgM-induced apoptosis, did not use the APO-1 receptor-ligand system because they failed to express APO-1 ligand mRNA. Taken together, our results suggest that malignant T and B cell lines may use APO-1 receptor-ligand-dependent and -independent antigen receptor-induced apoptosis pathways respectively. Similarly, differential pathways may be used by T and B cell subsets.