{"doi":"10.1016/j.celrep.2024.114283","title":"Regulation of Foxo1 expression is critical for central B cell tolerance and allelic exclusion","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.","journal":"Cell Reports","year":2024,"id":446837,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":364305,"name":"Anjelica M. Miranda","orcid":"0000-0002-8978-2816","position":1,"is_corresponding":false},{"id":1264476,"name":"Hadeel A. Khammash","orcid":null,"position":2,"is_corresponding":false},{"id":351700,"name":"Raul M. Torres","orcid":"0000-0002-5969-5957","position":3,"is_corresponding":false},{"id":489904,"name":"Roberta Pelanda","orcid":"0000-0001-8941-3941","position":4,"is_corresponding":false},{"id":1098191,"name":"Megan R. McCaleb","orcid":null,"position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:01:54.980444Z","pmid":"38796853","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}