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Apoptosis in B lymphocytes: The WEHI‐231 perspective
Author(s) -
GOTTSCHALK ALEXANDER R.,
QUINTANS JOSE
Publication year - 1995
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1995.2
Subject(s) - perspective (graphical) , apoptosis , microbiology and biotechnology , chemistry , psychology , cancer research , immunology , biology , computer science , biochemistry , artificial intelligence
Summary 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 G o /G 1 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.