Induction of apoptosis by dexamethasone in the B cell lineage.
The susceptibility to induction of apoptosis by the synthetic glucocorticoid, dexamethasone (Dex), was analysed at different stages of B cell maturation. Cells of the 70Z/3 pre-B cell line, expressing cytoplasmic mu chains, and LPS-stimulated 70Z/3 cells, expressing surface IgM, were used as a model of differentiation of pre-B cells into immature B cells. Cell proliferation and cell cycle progression were similarly inhibited by Dex (100 nM) in both naive 70Z/3 pre-B cells and in LPS-stimulated 70Z/3 cells. In contrast, Dex failed to affect apoptosis of naive 70Z/3 cells while it increased that of LPS-stimulated 70Z/3 cells. Splenic mature B lymphocytes were highly susceptible to Dex-induced apoptosis since subphysiological doses (5 nM) increased the frequency of apoptotic cells to more than 80%. On the other hand, the treatment of B lymphocytes with LPS, which led to proliferation and differentiation into immunoblasts, decreased the susceptibility to Dex-induced apoptosis. These effects were mediated by the glucocorticoid receptor since they were abrogated by the RU 486 antagonist. The response of B cells to glucocorticoids is thus dependent on their stage of differentiation.
Institut de Biochimie, CNRS ERS 0571, Université Paris-Sud, Orsay, France. karine.andreau@bbmpc.u-psud.fr
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Andréau
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Lemaire
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Souvannavong
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Adam
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000187:drug effects
D005938:Glucocorticoids; D008070:Lipopolysaccharides; D003907:Dexamethasone