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-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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / cytology*
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B-Lymphocytes / immunology
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Blotting, Southern
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Cell Differentiation / immunology*
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DNA-Binding Proteins / immunology
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DNA-Binding Proteins / metabolism
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Enzyme-Linked Immunosorbent Assay
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Flow Cytometry
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Forkhead Box Protein O1
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / immunology*
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Forkhead Transcription Factors / metabolism
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Gene Expression / immunology
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Gene Rearrangement, B-Lymphocyte / genetics
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Homeodomain Proteins / immunology
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Homeodomain Proteins / metabolism
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Immunohistochemistry
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Mice
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Mice, Mutant Strains
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Reverse Transcriptase Polymerase Chain Reaction
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Stem Cells / immunology
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Stem Cells / metabolism
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Transcription, Genetic / immunology
Substances
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DNA-Binding Proteins
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Foxo1 protein, mouse
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Homeodomain Proteins
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Rag2 protein, mouse
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RAG-1 protein