ArticleCell reports2024
Regulation of Foxo1 expression is critical for central B cell tolerance and allelic exclusion.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Transcriptomic characterization of transitional B cells reveals four subsets with perturbed activation profiles in scleroderma.iScience · 2026Article
- RAG1/2 expression in IGH-switched follicular lymphoma associated with transformation to high-grade B-cell lymphoma.Leukemia · 2026Article
- FNIP1 Modulates B Cell Receptor Signaling Strength by Coordinating Metabolism During Development.bioRxiv : the preprint server for biology · 2026Article
- Studies of Foxo1 over the Past 25 Years: Mechanisms of Insulin Resistance and Glucose Dysregulation.Cells · 2026Review
- Biphasic control of the B cell transcriptome by mTORC1 and GSK3.Cell reports · 2025Article
- B-cell Receptor Silencing Reveals the Origin and Dependencies of High-Grade B-cell Lymphomas with MYC and BCL2 Rearrangements.Blood cancer discovery · 2025Article
- CD19 Deficiency Leads to Dysregulation of Phosphoinositide 3-Kinase-Protein Kinase B (Journal of clinical practice and research · 2025Article
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Authors and funding
5 authors.
Funding
Abstract
Resolving the molecular mechanisms of central B cell tolerance might unveil strategies that prevent autoimmunity. Here, using a mouse model of central B cell tolerance in which Forkhead box protein O1 (Foxo1) is either deleted or over-expressed in B cells, we show that deleting Foxo1 blocks receptor editing, curtails clonal deletion, and decreases CXCR4 expression, allowing high-avidity autoreactive B cells to emigrate to the periphery whereby they mature but remain anergic and short lived. Conversely, expression of degradation-resistant Foxo1 promotes receptor editing in the absence of self-antigen but leads to allelic inclusion. Foxo1 over-expression also restores tolerance in autoreactive B cells harboring active PI3K, revealing opposing roles of Foxo1 and PI3K in B cell selection. Overall, we show that the transcription factor Foxo1 is a major gatekeeper of central B cell tolerance and that PI3K drives positive selection of immature B cells and establishes allelic exclusion by suppressing Foxo1.
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