Holmes Melissa L, Carotta Sebastian, Corcoran Lynn M, Nutt Stephen L
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Genes Dev. 2006 Apr 15;20(8):933-8. doi: 10.1101/gad.1396206.
Early B-lymphopoiesis requires the growth-factor receptors, IL-7R and Flt3, and the activity of a number of transcription factors. One factor, Pax5, is required for commitment to the B-cell lineage, although the molecular mechanism by which this occurs is unknown. We demonstrate here that an important function of Pax5 is to repress Flt3 transcription in B-cell progenitors, as Pax5-deficient pro-B cells express abundant Flt3 that is rapidly silenced upon the reintroduction of Pax5, whereas enforced expression of Flt3 in wild-type progenitors significantly impairs B-cell development. These findings demonstrate that the repression of Flt3 by Pax5 is essential for normal B-lymphopoiesis.
早期B淋巴细胞生成需要生长因子受体IL-7R和Flt3，以及多种转录因子的活性。一种转录因子Pax5是B细胞谱系定向分化所必需的，尽管其发生的分子机制尚不清楚。我们在此证明，Pax5的一个重要功能是在B细胞祖细胞中抑制Flt3转录，因为缺乏Pax5的前B细胞表达大量Flt3，而重新引入Pax5后Flt3会迅速沉默，而在野生型祖细胞中强制表达Flt3会显著损害B细胞发育。这些发现表明，Pax5对Flt3的抑制作用对于正常的B淋巴细胞生成至关重要。
