Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation

作者：Dengler Hart S; Baracho Gisele V; Omori Sidne A; Bruckner Shane; Arden Karen C; Castrillon Diego H; DePinho Ronald A; Rickert Robert C^*

来源：Nature Immunology, 2008, 9(12): 1388-1398.

DOI：10.1038/ni.1667

The transcription factors Foxo1, Foxo3 and Foxo4 modulate cell fate 'decisions' in diverse systems. Here we show that Foxo1-dependent gene expression was critical at many stages of B cell differentiation. Early deletion of Foxo1 caused a substantial block at the pro-B cell stage due to a failure to express interleukin 7 receptor-alpha. Foxo1 inactivation in late pro-B cells resulted in an arrest at the pre-B cell stage due to lower expression of the recombination-activating genes Rag1 and Rag2. Deletion of Foxo1 in peripheral B cells led to fewer lymph node B cells due to lower expression of L-selectin and failed class-switch recombination due to impaired upregulation of the gene encoding activation-induced cytidine deaminase. Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function.

• 出版日期2008-12
• 单位河北医科大学