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Second‐messenger pathways involved in the regulation of survival in germinal‐centre B cells and in burkitt lymphoma lines
Author(s) -
Knox Kirstine A.,
Finney Michael,
Milner Anne E.,
Gregory Christopher D.,
Wakelam Michael J. O.,
Michell Robert H.,
Gordon John
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910520622
Subject(s) - germinal center , lymphoma , burkitt's lymphoma , messenger rna , second messenger system , cancer research , biology , medicine , immunology , signal transduction , microbiology and biotechnology , genetics , b cell , gene , antibody
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 ([Ca 2+ ],) and protein kinase C (PKC). Anti‐lg was found to mobilize Ca 2+ in group‐l cells. Pre‐incubation with the Ca 2‐ chelator EGTA partially reduced apoptosis induced by anti‐lg or by Ca 2+ ionophore in group‐l BL cells. Activation of PKC with phorbol ester reduced such Ca 2+ ‐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 [Ca 2+ ], 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.