Abstract
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-α. 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.
Original language | English (US) |
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Pages (from-to) | 1388-1398 |
Number of pages | 11 |
Journal | Nature Immunology |
Volume | 9 |
Issue number | 12 |
DOIs | |
State | Published - 2008 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology