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.
Peter
M E
ME
Tumor Immunology Program, German Cancer Research Center, Heidelberg, Germany.
Dhein
J
J
Ehret
A
A
Hellbardt
S
S
Walczak
H
H
Moldenhauer
G
G
Krammer
P H
PH
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D006801:Humans; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology*
D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor