Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.
Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.
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Foxo转录因子（Foxo1、Foxo3、Foxo4）在多种系统中调节细胞命运的决定。在此我们表明，Foxo1依赖的基因表达在B细胞分化的多个阶段至关重要。Foxo1的早期缺失由于白细胞介素7受体α（IL - 7Rα）表达失败，在祖B细胞阶段导致严重阻滞。晚期祖B细胞中Foxo1失活由于Rag1和Rag2表达降低，导致在前B细胞阶段停滞。外周B细胞中Foxo1的缺失由于L - 选择素表达减少导致淋巴结B细胞减少，并且由于Aicda上调受损导致类别转换重组失败。因此，Foxo1调控一个对早期B细胞发育和外周B细胞功能至关重要的转录程序。
The Foxo transcription factors (Foxo1, Foxo3, Foxo4) modulate cell fate decisions in diverse systems. Here we show that Foxo1-dependent gene expression was critical at multiple stages of B cell differentiation. Early deletion of Foxo1 caused a severe block at the pro-B cell stage, due to a failure to express interleukin 7 receptor α (IL-7Rα). Foxo1 inactivation in late pro-B cells resulted in an arrest at the pre-B cell stage due to a reduction in Rag1 and Rag2 expression. Deletion of Foxo1 in peripheral B cells led to fewer lymph node B cells due to reduced L-selectin expression, and failed class switch recombination due to impaired Aicda upregulation. Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function.