Regulation of bcl-x(L) expression and Fas susceptibility in mouse B cells by CD40 ligation, surface IgM crosslinking and IL-4

被引:20
作者
Koizumi, T [1 ]
Wang, J [1 ]
Suzuki, Y [1 ]
Masuda, K [1 ]
Watanabe, T [1 ]
机构
[1] KYUSHU UNIV, MED INST BIOREGULAT, FUKUOKA 81282, JAPAN
关键词
CD40; Fas/Apo-1/CD95; apoptosis; bcl-x(L);
D O I
10.1016/S0161-5890(96)00084-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
CD40 is one of the key molecules involved in the survival, growth and differentiation of B lymphocytes. In contrast, Fas (Apo-1, CD95) mediates apoptosis of a variety of cell types, including lymphocytes. Recent studies have found that Fas expression on mouse B cells could be strongly induced by CD40 ligation, a helper T cell-derived signal. Here, evidence is provided that CD40 ligation induced two distinct signals: one leading to the upregulation of Fas and the other leading to the enhanced Fas susceptibility. B lymphoma cell lines, CH31 and WEHI279, expressed Fas on cell surfaces, but were resistant to anti-Fas antibody (Ab) induced apoptosis. Treatment with CD40 ligand (CD40L), however, greatly enhanced Fas susceptibility of these cells. Similarly, normal splenic B cells became highly susceptible to Fas-mediated apoptosis following prolonged signaling through CD40. While CD40 ligation enhanced Fas-mediated apoptosis, stimulation with anti-IgM and IL-4 partially protected CD40L-activated B cells from Fas-mediated apoptosis. It was found that bcl-x(L) gene expression in normal splenic B cells was induced drastically by treatment with anti-IgM and IL-4, but not CD40L. By contrast, the expression of bcl-2 or bar was not significantly affected by these treatments. Moreover, in three of the four B lymphoma cell lines tested, Fas susceptibility correlated with the status of bcl-x(L) expression. The data suggest that an increase in bcl-x(L) expression may protect B cells from Fas-mediated apoptosis. (C) 1997 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:1247 / 1253
页数:7
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