Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development
Instructive role of the transcription factor E2A in early B lymphopoiesis and germinal center B cell development
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DOI：
10.1016/j.immuni.2008.04.014
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发表时间：
2008-06-01
期刊：
影响因子：
32.4
通讯作者：
Busslinger, Meinrad
中科院分区：
文献类型：
--
作者：
Kwon, Kyongrim;Hutter, Caroline;Busslinger, Meinrad
转录因子E2A控制B淋巴生成的起始，在E2A缺陷小鼠中，B淋巴生成在pre-pro-B细胞阶段被阻止。在这里，我们通过条件诱变证明E2A对于骨髓中前B细胞、前B细胞和未成熟B细胞的发育至关重要。然而，E2A对于周围淋巴器官成熟B细胞和浆细胞的产生是必不可少的。相比之下，生发中心B细胞在缺乏E2A的情况下发育受损，尽管AID正常表达和类转换重组。分子分析表明，E2A不仅是启动和维持前B细胞中Ebf1、Pax5和B细胞基因程序表达所必需的。值得注意的是，来自lkzf1位点的Pax5早熟转录促进了E2A缺陷小鼠的前B细胞发育，这表明在缺乏E2A的情况下，Pax5异位表达足以激活体内B淋巴细胞转录程序。
The transcription factor E2A controls the initiation of B lymphopoiesis, which is arrested at the pre-pro-B cell stage in E2A-deficient mice. Here, we demonstrate by conditional mutagenesis that E2A is essential for the development of pro-B, pre-B, and immature B cells in the bone marrow. E2A is, however, dispensable for the generation of mature B cells and plasma cells in peripheral lymphoid organs. In contrast, germinal center B cell development is impaired in the absence of E2A despite normal AID expression and class-switch recombination. Molecular analysis revealed that E2A is required not only for initiating but also for maintaining the expression of Ebf1, Pax5, and the B cell gene program in pro-B cells. Notably, precocious Pax5 transcription from the lkzf1 locus promotes pro-B cell development in E2A-deficient mice, demonstrating that ectopic Pax5 expression is sufficient to activate the B lymphoid transcription program in vivo in the absence of E2A.