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

Abstract

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.