Overexpression of Bcl-2 does not rescue impaired B lymphopoiesis in IL-7 receptor-deficient mice but can enhance survival of mature B cells
Overexpression of Bcl-2 does not rescue impaired B lymphopoiesis in IL-7 receptor-deficient mice but can enhance survival of mature B cells
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DOI：
10.1093/intimm/10.9.1367
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发表时间：
1998-09-01
影响因子：
4.4
通讯作者：
Strasser, A
中科院分区：
文献类型：
--
作者：
Maraskovsky, E;Peschon, JJ;Strasser, A
IL-7受体缺陷(IL-7R(-/-))小鼠是B和T淋巴细胞生成早期缺陷细胞产生的结果，在骨髓中，在前B细胞向前B细胞阶段的过渡阶段，B细胞的发育受到不完全的阻碍。因此，IL-7R(-/-)小鼠的外周淋巴器官含有异常低数量的成熟表面(S)Ig表达的B细胞，并伴随着未成熟SLG(-)B细胞的相对增加。在IL-7R(-/-)小鼠中转基因表达抗凋亡蛋白Bcl2，挽救了T细胞发育和成熟T细胞功能的缺陷。本研究表明，Bcl2的结构性表达不能挽救IL-7R(-/-)小鼠的B淋巴细胞生成，但可以提高那些逃脱发育停滞的成熟B细胞的存活率。因此，IL-7R信号在B淋巴样细胞中的重要作用是Bcl2所不能替代的，这表明在B淋巴系中，IL-7R信号是促进细胞分裂和/或抑制Eel-a不敏感的细胞凋亡途径所必需的。
IL-7 receptor-deficient (IL-7R(-/-)) mice are lymphopenic as a result of defective cell production at early steps in both B and T lymphopoiesis, In the bone marrow, there is an incomplete block in B cell development at the transition from the pro-B to the pre-B cell stage. As a consequence, peripheral lymphoid organs of IL-7R(-/-) mice contain abnormally low numbers of mature surface (s) Ig-expressing B cells and this is accompanied by a relative increase in immature slg(-) B cells. Transgenic expression of the anti-apoptotic protein Bcl-2 in IL-7R(-/-) mice rescues the defect in T cell development and in mature T cell function. The present report shows that constitutive expression of Bcl-2 is incapable of rescuing B lymphopoiesis in IL-7R(-/-) mice but can enhance survival of those mature B cells which escape the developmental arrest. Thus the essential role of IL-7R signaling in B lymphoid cells cannot be replaced by Bcl-2, indicating that in B lymphopoiesis IL-7R signaling is necessary for promoting cell division and/or for inhibiting a Eel-a-insensitive pathway to apoptosis.