Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
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DOI：
10.1038/ni.1626
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发表时间：
2008-08-01
影响因子：
30.5
通讯作者：
Singh, Harinder
中科院分区：
文献类型：
--
作者：
Reynaud, Damien;Demarco, Ignacio A.;Singh, Harinder
转录因子Ikaros对B细胞发育至关重要。然而，其在B细胞命运的规范和承诺的分子功能仍然难以捉摸。我们发现转录因子EBF恢复了Ikaros缺陷型造血祖细胞的CD 19（+）pro-B细胞的生成。值得注意的是，这些前B细胞尽管具有转录因子EBF和Pax 5的正常表达，但不定向于B细胞命运。他们也未能在免疫球蛋白重链位点重组可变基因片段。Ikaros通过诱导重组激活基因的表达以及通过控制可变基因片段的可及性和免疫球蛋白重链基因座的压缩来促进重链基因重排。因此，Ikaros是调节B细胞命运定型和免疫球蛋白重链基因重组的网络的专性组成部分。
The transcription factor Ikaros is essential for B cell development. However, its molecular functions in B cell fate specification and commitment have remained elusive. We show here that the transcription factor EBF restored the generation of CD19(+) pro-B cells from Ikaros-deficient hematopoietic progenitors. Notably, these pro-B cells, despite having normal expression of the transcription factors EBF and Pax5, were not committed to the B cell fate. They also failed to recombine variable gene segments at the immunoglobulin heavy-chain locus. Ikaros promoted heavy-chain gene rearrangements by inducing expression of the recombination-activating genes as well as by controlling accessibility of the variable gene segments and compaction of the immunoglobulin heavy-chain locus. Thus, Ikaros is an obligate component of a network that regulates B cell fate commitment and immunoglobulin heavy-chain gene recombination.