Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice.
Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice.
复制标题
bcl-2 转基因小鼠胸腺细胞凋亡和阴性抗原选择的抑制。
DOI：
10.1073/pnas.89.15.7003
复制
发表时间：
1992
影响因子：
11.1
通讯作者：
Reed,JC
中科院分区：
文献类型：
--
作者：
Siegel,RM;Katsumata,M;Miyashita,T;Louie,DC;Greene,MI;Reed,JC
在人类滤泡性B细胞淋巴瘤中过度表达的bcl-2基因已被发现通过抑制细胞凋亡或程序性细胞死亡来延长细胞寿命。然而，Bcl-2蛋白在淋巴细胞发育中的生理作用尚不清楚。我们已经建立了一个转基因小鼠系，表达高水平的Bcl-2蛋白质在皮质和髓质胸腺细胞，破坏了正常的模式表达该基因。我们发现，在这些小鼠中，未成熟的胸腺细胞成为抵抗皮质类固醇和钙离子载体介导的细胞凋亡。与对照组相比，未处理的胸腺细胞在悬浮培养中也表现出存活优势。此外，bcl-2的过表达使一定比例的胸腺细胞和外周T细胞逃避克隆缺失的过程，这通常会在胸腺细胞成熟过程中消除自身反应性T细胞。这些发现暗示Bcl-2蛋白在调节成熟胸腺细胞的寿命和抗原选择过程。
The bcl-2 gene, which is overexpressed in human follicular B-cell lymphomas, has been found to extend cellular lifespan through inhibition of apoptosis, or programmed cell death. However, the physiological role of the Bcl-2 protein in lymphocyte development is unclear. We have established a transgenic mouse line that expresses high levels of the Bcl-2 protein in both cortical and medullary thymocytes, disrupting the normal pattern of expression of this gene. We found that in these mice, immature thymocytes became resistant to apoptosis mediated by corticosteroids and calcium ionophores. Untreated thymocytes also exhibited a survival advantage in suspension cultures compared with controls. In addition, overexpression of bcl-2 enabled a proportion of thymocytes and peripheral T cells to escape the process of clonal deletion, which normally eliminates self-reactive T cells during thymocyte maturation. These findings implicate the Bcl-2 protein in regulating the lifespan of maturing thymocytes and in the antigenic-selection process.