Hu Hui, Wang Bin, Borde Madhuri, Nardone Julie, Maika Shan, Allred Laura, Tucker Philip W, Rao Anjana
Department of Pathology, Harvard Medical School, CBR Institute for Biomedical Research, Boston, Massachusetts 02115, USA.
Nat Immunol. 2006 Aug;7(8):819-26. doi: 10.1038/ni1358. Epub 2006 Jul 2.
Forkhead transcription factors are key participants in development and immune regulation. Here we demonstrate that absence of the gene encoding the forkhead transcription factor Foxp1 resulted in a profound defect in early B cell development. Foxp1 deficiency was associated with decreased expression of all B lineage genes in B220+ fetal liver cells as well as with a block in the transition from pro-B cell to pre-B cell involving diminished expression of recombination-activating genes 1 and 2. Foxp1 bound to the Erag enhancer and was involved in controlling variable-(diversity)-joining recombination of the gene encoding immunoglobulin heavy chain in a B cell lineage-specific way. Our results identify Foxp1 as an essential participant in the transcriptional regulatory network of B lymphopoiesis.
叉头转录因子是发育和免疫调节的关键参与者。在此我们证明，编码叉头转录因子Foxp1的基因缺失导致早期B细胞发育出现严重缺陷。Foxp1缺陷与B220⁺胎肝细胞中所有B谱系基因的表达降低有关，也与从pro-B细胞到pre-B细胞的转变受阻有关，这涉及重组激活基因1和2的表达减少。Foxp1与Erag增强子结合，并以B细胞谱系特异性方式参与控制免疫球蛋白重链编码基因的可变（多样性）连接重组。我们的结果确定Foxp1是B淋巴细胞生成转录调控网络的重要参与者。
