The development of early and mature B cells is impaired in mice deficient for the Ets-1 transcription factor
The development of early and mature B cells is impaired in mice deficient for the Ets-1 transcription factor
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DOI：
10.1002/eji.200425352
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发表时间：
2004-11-01
影响因子：
5.4
通讯作者：
Bories, JC
中科院分区：
文献类型：
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作者：
Eyquem, S;Chemin, K;Bories, JC
Ets-1转录因子对于自然杀伤细胞和T细胞系的正常发育是必不可少的；然而，它在B细胞发育中的作用仍然知之甚少。为了解决这个问题，我们使用基因打靶来灭活小鼠的ETS-1(ETS-1(-/-))。我们在这里表明，在ETS-1(-/-)小鼠中，B细胞前体的发育，特别是需要前B细胞受体功能的步骤，是有缺陷的。分析了用ETS-1(-/-)胎肝细胞重组RAG2缺陷小鼠的外周B细胞亚群。在这种ETS-1(-/-)嵌合小鼠中，B细胞前体发育成IgM/IGD承载细胞，但B-1a细胞以及脾的过渡区-2和边缘区B细胞亚群缺失。在B细胞受体刺激下，ETS-1(-/-)脾B细胞不表达CD69和CD25激活标志物。此外，尽管ERK和JNK信号通路被激活，但Ets-1缺陷的B细胞不会在BCR参与后增殖和死亡。这些结果表明，Ets-1失活的作用不仅限于终末8细胞分化阶段，而且还影响早期B细胞亚群的发育和功能。
The Ets-1 transcription factor is essential for normal development of the natural killer and T cell lineages; however, its role in B cell development remains poorly understood. To address this issue, we used gene targeting to inactivate Ets-1 in mice (Ets-1(-/-)). We show here that the development of B cell precursors, particularly steps requiring pre-B cell receptor function, is defective in Ets-1(-/-) mice. Peripheral B cell subsets were analyzed in RAG2-deficient mice reconstituted with Ets-1(-/-) fetal liver cells. In such Ets-1(-/-)chimeric mice, B cell precursors develop into IgM/IgD-bearing cells, but B-1a cells as well as transitional-2 and marginal zone B cell subsets of the spleen are absent. In response to B cell receptor stimulation, Ets-1(-/-) splenic B cells fail to express the CD69 and CD25 activation markers. Furthermore, despite activation of ERK and JNK signaling pathways, Ets-1-deficient B cells do not proliferate and die following BCR engagement. These findings demonstrate that the effect of Ets-1 inactivation is not restricted to the terminal 8 cell differentiation stage, but also affects the development and function of earlier B cell subsets.