Second‐messenger pathways involved in the regulation of survival in germinal‐centre B cells and in burkitt lymphoma lines

Kirstine A. Knox*, Michael Finney, Anne E. Milner, Christopher D. Gregory, Michael J.O. Wakelam, Robert H. Michell, John Gordon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)


Spontaneous apoptosis in germinal‐centre (G.C) B cells can be prevented by treatment with anti‐immunoglobulin (Ig). By contrast, susceptible group‐l Burkitt lymphoma (BL) cells can be driven to apoptosis by anti‐lg. The second‐messenger pathways involved in the regulation of apoptosis in GC B lymphocytes and in BL cell lines were studied using pharmacological agonists or inhibitors of intracellular calcium ([Ca2+],) and protein kinase C (PKC). Anti‐lg was found to mobilize Ca2+ in group‐l cells. Pre‐incubation with the Ca2‐ chelator EGTA partially reduced apoptosis induced by anti‐lg or by Ca2+ionophore in group‐l BL cells. Activation of PKC with phorbol ester reduced such Ca2+‐driven programmed cell death (PCD) to control levels of apoptosis. Apoptosis in group‐l BL cell lines could also be triggered by the kinase inhibitors staurosporine and Ro‐31 ‐8220 at concentrations selective for PKC activity. Expression of the bcl‐2 protein in BL group‐l cells following gene transfer affords protection from apoptosis induced by ionomy‐cin or anti‐lg. In the present study, bcl‐2 was additionally found to protect from apoptosis driven by staurosporine. The high levels of spontaneous apoptosis exhibited fay normal GC 6 cells were reduced, but not abrogated, by co‐culture with phorbol ester. These results indicate that, in group‐l BL cells, imbalance in the phosphoinositide pathway of signalling, in favour of [Ca2+], and away from PKC, results in apoptosis: constitutive phosphorylation of key proteins by PKC may therefore suppress apoptosis in BL as well as in GC B cells. © 1992 Wiley‐Liss, Inc.

Original languageEnglish
Pages (from-to)959-966
Number of pages8
JournalInternational Journal of Cancer
Issue number6
Publication statusPublished - 2 Dec 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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