Apoptosis in B lymphocytes: the WEHI-231 perspective.
In this review we summarize recent work on the molecular basis of apoptosis in the murine B cell lymphoma WEHI-231. WEHI-231 cells undergo apoptosis in response to antigen receptor cross-linking with anti-Ig reagents. Death is specifically triggered via surface IgM (sIgM); cross-linking sIgD, Ia or FcR has no effect. Apoptosis is preceded by growth arrest in the G0/G1 phase of the cell cycle and may not occur in all currently available WEHI-231 sublines. The continuous passage of WEHI-231 cells in different laboratories has yielded variants that differ greatly in their response to anti-Ig treatment because apoptotic cells tend to be negatively selected in culture. Resistant and susceptible variants undergo growth arrest in response to anti-Ig but only susceptible cells go on to die by apoptosis. Cells resistant to anti-Ig have intact apoptotic machinery as indicated by their susceptibility to dexamethasone, irradiation and other treatments. However, anti-Ig-resistant cells are also resistant to apoptosis induced by the immunosuppressants cyclosporin A, FK-506 and rapamycin. We discuss the experimental evidence indicating that the apoptotic machinery in WEHI-231 cells is pre-activated but under constant negative regulation by short-lived protein inhibitors. Inhibition is removed by a mediator released in response to anti-Ig treatment in susceptible sublines. The mediator of death is the sphingosine derivative, ceramide, presumably produced by membrane sphingomyelinases activated by anti-Ig. A hypothetical model on how ceramide kills WEHI-231 is presented.
Gottschalk
A R
AR
Department of Pathology and Cancer Research Center, University of Chicago, IL 60637, USA.
Quintáns
J
J
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002518:Ceramides / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018448:Models, Immunological; D006377:T-Lymphocytes, Helper-Inducer; D014407:Tumor Cells, Cultured
D001323:Autoantibodies; D002518:Ceramides; D008070:Lipopolysaccharides