BAX和BAK在B细胞稳态维持及自身免疫性疾病预防中的关键作用。
Essential role of BAX,BAK in B cell homeostasis and prevention of autoimmune disease.
作者信息
Takeuchi Osamu, Fisher Jill, Suh Heikyung, Harada Hisashi, Malynn Barbara A, Korsmeyer Stanley J
机构信息
Howard Hughes Medical Institute, Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Proc Natl Acad Sci U S A. 2005 Aug 9;102(32):11272-7. doi: 10.1073/pnas.0504783102. Epub 2005 Jul 29.
Abstract
B cell homeostasis is maintained by a balance between the continual generation of new cells and their elimination. Here we show proapoptotic BCL-2 family members BAX and BAK are essential for regulating the number of B cells at both immature and mature developmental stages. BAX and BAK are critical mediators of B cell death induced by multiple stimuli. In addition, BAX- and BAK-deficient B cells display defective cell cycle progression to B cell receptor crosslinking and lipopolysaccharide, but not to CpG-DNA. Furthermore, inducible deletion of Bax and Bak in adult mice results in the development of severe autoimmune disease.
摘要
B细胞的稳态通过新细胞的持续产生与其清除之间的平衡来维持。在此我们表明，促凋亡的BCL-2家族成员BAX和BAK对于在未成熟和成熟发育阶段调节B细胞数量至关重要。BAX和BAK是多种刺激诱导的B细胞死亡的关键介质。此外，缺乏BAX和BAK的B细胞在B细胞受体交联和脂多糖刺激下，而非CpG-DNA刺激下，细胞周期进程存在缺陷。此外，成年小鼠中Bax和Bak的诱导性缺失会导致严重自身免疫性疾病的发生。
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