Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.
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.
Dengler
Hart S
HS
Program of Inflammatory Disease Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Baracho
Gisele V
GV
Omori
Sidne A
SA
Bruckner
Shane
S
Arden
Karen C
KC
Castrillon
Diego H
DH
DePinho
Ronald A
RA
Rickert
Robert C
RC
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D015139:Blotting, Southern; D002454:Cell Differentiation / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D015322:Gene Rearrangement, B-Lymphocyte / Q000235:genetics; D018398:Homeodomain Proteins / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008817:Mice, Mutant Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology
D004268:DNA-Binding Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D018398:Homeodomain Proteins; C499308:Rag2 protein, mouse; C064658:RAG-1 protein