Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12.
Induction of early B cell factor (EBF) and multiple B lineage genes by the basic helix-loop-helix transcription factor E12.
复制标题
DOI：
10.1084/jem.188.4.699
复制
发表时间：
1998-08-17
期刊：
影响因子：
--
通讯作者：
Murre C
中科院分区：
文献类型：
--
作者：
Kee BL;Murre C
由E2A和早期B细胞因子（EBF）基因编码的转录因子是B淋巴细胞正常发育所必需的。然而，E2A和EBF缺陷型小鼠中B谱系细胞的缺失使得确定这些蛋白质之间的功能或关系变得困难。我们报道了一种新型模型系统的鉴定，在该系统中可以研究E2A和EBF在调节多种B谱系特征中的作用。我们发现70Z/3前B淋巴细胞向具有巨噬细胞样表型的细胞的转化与E2A和EBF的缺失有关。此外，我们表明在这种巨噬细胞系中E2A蛋白E12的异位表达导致许多B谱系基因的诱导，包括EBF、IL7Rα、λ5和Rag - 1，以及在有丝分裂原刺激下诱导κ轻链的能力。EBF的激活可能是E12在调节B谱系表型中的关键功能之一，因为单独表达EBF会导致一部分E12可诱导特征的激活。我们的数据表明，在这种巨噬细胞系的背景下，E12诱导EBF的表达，并且这些转录因子共同协调调节众多与B谱系相关的基因。
The transcription factors encoded by the E2A and early B cell factor (EBF) genes are required for the proper development of B lymphocytes. However, the absence of B lineage cells in E2A- and EBF-deficient mice has made it difficult to determine the function or relationship between these proteins. We report the identification of a novel model system in which the role of E2A and EBF in the regulation of multiple B lineage traits can be studied. We found that the conversion of 70Z/3 pre-B lymphocytes to cells with a macrophage-like phenotype is associated with the loss of E2A and EBF. Moreover, we show that ectopic expression of the E2A protein E12 in this macrophage line results in the induction of many B lineage genes, including EBF, IL7Rα, λ5, and Rag-1, and the ability to induce κ light chain in response to mitogen. Activation of EBF may be one of the critical functions of E12 in regulating the B lineage phenotype since expression of EBF alone leads to the activation of a subset of E12-inducible traits. Our data demonstrate that, in the context of this macrophage line, E12 induces expression of EBF and together these transcription factors coordinately regulate numerous B lineage–associated genes.