Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells.
Loss of the pro-apoptotic BH3-only Bcl-2 family member Bim inhibits BCR stimulation-induced apoptosis and deletion of autoreactive B cells.
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DOI：
10.1084/jem.20030411
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发表时间：
2003-10-06
影响因子：
15.3
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
Enders, A;Bouillet, P;Puthalakath, H;Xu, YK;Tarlinton, DM;Strasser, A
在发育过程中，编码抗原受体的基因的随机过程总是产生能够识别自身抗原的B和T淋巴细胞。已经发展了几种机制来防止这些细胞的激活和伴随的自身免疫性疾病的发展。一种这样的机制是在不存在T细胞帮助的情况下通过B细胞抗原受体（BCR）的接合在发育或成熟的B细胞中诱导凋亡。在这里，我们报告说，B淋巴细胞缺乏促凋亡Bcl-2家族成员Bim是难凋亡诱导的BCR结扎在体外。Bim的缺失也抑制了体内自身反应性B细胞在两个B细胞耐受转基因系统中的缺失。Bim缺失阻止了可溶性自身抗原诱导的自身反应性B细胞的缺失，并促进了在膜结合自身抗原存在下发展的自身反应性B细胞的积累，尽管它们的数量与无抗原小鼠相比显著降低。从机制上讲，我们确定BCR连接促进Bim与Bcl-2的相互作用，抑制其存活功能。这些发现表明Bim在BCR介导的细胞凋亡和B淋巴细胞缺失中是一个关键的参与者。
During development, the stochastic process assembling the genes encoding antigen receptors invariably generates B and T lymphocytes that can recognize self-antigens. Several mechanisms have evolved to prevent the activation of these cells and the concomitant development of autoimmune disease. One such mechanism is the induction of apoptosis in developing or mature B cells by engagement of the B cell antigen receptor (BCR) in the absence of T cell help. Here we report that B lymphocytes lacking the pro-apoptotic Bcl-2 family member Bim are refractory to apoptosis induced by BCR ligation in vitro. The loss of Bim also inhibited deletion of autoreactive B cells in vivo in two transgenic systems of B cell tolerance. Bim loss prevented deletion of autoreactive B cells induced by soluble self-antigen and promoted accumulation of self-reactive B cells developing in the presence of membrane-bound self-antigen, although their numbers were considerably lower compared with antigen-free mice. Mechanistically, we determined that BCR ligation promoted interaction of Bim with Bcl-2, inhibiting its survival function. These findings demonstrate that Bim is a critical player in BCR-mediated apoptosis and in B lymphocyte deletion.
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影响因子：
64.8
作者：
RATHMELL, JC;COOKE, MP;GOODNOW, CC
通讯作者：
GOODNOW, CC
影响因子：
64.5
作者：
HARTLEY, SB;COOKE, MP;GOODNOW, CC
通讯作者：
GOODNOW, CC
DOI：
10.1084/jem.177.4.999
发表时间：
1993-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gay D;Saunders T;Camper S;Weigert M
通讯作者：
Weigert M
影响因子：
32.4
作者：
CYSTER, JG;GOODNOW, CC
通讯作者：
GOODNOW, CC
影响因子：
64.8
作者：
ERIKSON, J;RADIC, MZ;WEIGERT, M
通讯作者：
WEIGERT, M