ER stress is involved in B cell antigen receptor ligation-induced apoptosis
ER stress is involved in B cell antigen receptor ligation-induced apoptosis
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DOI：
10.1016/j.bbrc.2007.10.137
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发表时间：
2008-01-04
影响因子：
3.1
通讯作者：
Tsubata, Takeshi
中科院分区：
文献类型：
--
作者：
Yan, Bin-Cheng;Adachi, Takahiro;Tsubata, Takeshi
B细胞抗原受体（BCR）连接后的B细胞凋亡在消除自身反应性B细胞中起作用。以前，BCR连接显示诱导参与未折叠蛋白反应（UPR）的分子的表达。然而，UPR在BCR介导的细胞凋亡中的作用知之甚少。在这里，我们证明了当BCR连接诱导B细胞系WEHI-231和小鼠脾B细胞凋亡时，各种UPR分子的激活被诱导。BCR连接诱导的UPR在这些细胞中通过CD 40的存活信号传导而减弱。当BiP过表达抑制WEHI-231细胞中的UPR时，p38 MAPK的激活被阻断，凋亡减少。此外，p38 MAPK抑制剂SB 203580减少BCR连接诱导的细胞凋亡。这些结果表明，UPR参与BCR连接诱导的细胞凋亡，并且p38 MAPK在B细胞的UPR过程中对细胞凋亡至关重要。(c)2007年爱思唯尔公司All rights reserved.
Apoptosis of B cells upon ligation of the B cell antigen receptor (BCR) plays a role in elimination of self-reactive B cells. Previously, BCR ligation was shown to induce expression of the molecules involved in the unfolded protein response (UPR). However, the role of the UPR in BCR-mediated apoptosis is poorly understood. Here, we demonstrate that activation of various UPR molecules are induced when BCR ligation induces apoptosis in the B cell line WEHI-231 and mouse spleen B cells. BCR ligation-induced UPR is attenuated by survival signaling through CD40 in these cells. When overexpression of BiP suppresses the UPR in WEHI-231 cells, activation of p38 MAPK is blocked and apoptosis is reduced. Moreover, the p38 MAPK inhibitor SB203580 reduces BCR ligation-induced apoptosis. These results suggest that the UPR is involved in BCR ligation-induced apoptosis and that p38 MAPK is crucial for apoptosis during the UPR in B cells. (c) 2007 Elsevier Inc. All rights reserved.