{"doi":"10.4049/jimmunol.2200639","title":"CARD19, a Novel Regulator of the TAK1/NF-κB Pathway in Self-Reactive B Cells","abstract":"The caspase recruitment domain family member (CARD)11-Bcl10-Malt1 signalosome controls TGF-β-activated kinase 1 (TAK1) activation and regulates BCR-induced NF-κB activation. In this study, we discovered that CARD19 interacted with TAK1 and inhibited TAB2-mediated TAK1 ubiquitination and activation. Although CARD19 deficiency in mice did not affect B cell development, it enhanced clonal deletion, receptor editing, and anergy of self-reactive B cells, and it reduced autoantibody production. Mechanistically, CARD19 deficiency increased BCR/TAK1-mediated NF-κB activation, leading to increased expression of transcription factors Egr2/3, as well as the E3 ubiquitin ligases c-Cbl/Cbl-b, which are known inducers of B cell tolerance in self-reactive B cells. RNA sequencing analysis revealed that although CARD19 deficiency did not affect the overall Ag-induced gene expression in naive B cells, it suppressed BCR signaling and increased hyporesponsiveness of self-reactive B cells. As a result, CARD19 deficiency prevented Bm12-induced experimental systemic lupus erythematosus. In summary, CARD19 negatively regulates BCR/TAK1-induced NF-κB activation and its deficiency increases Egr2/3 and c-Cbl/Cbl-b expression in self-reactive B cells, thereby enhancing B cell tolerance.","journal":"The Journal of Immunology","year":2023,"id":376695,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9567,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":295121,"name":"Mei Yu","orcid":"0000-0002-2140-8756","position":1,"is_corresponding":false},{"id":1139888,"name":"Yuhong Chen","orcid":"0000-0002-1359-1597","position":2,"is_corresponding":false},{"id":1140248,"name":"Liquan Xue","orcid":null,"position":3,"is_corresponding":false},{"id":810160,"name":"Wen Zhu","orcid":"0000-0002-7734-9943","position":4,"is_corresponding":false},{"id":731912,"name":"Guoping Fu","orcid":null,"position":5,"is_corresponding":false},{"id":1140249,"name":"Stephan W. Morris","orcid":null,"position":6,"is_corresponding":false},{"id":731296,"name":"Renren Wen","orcid":"0000-0003-2420-8212","position":7,"is_corresponding":false},{"id":295122,"name":"Demin Wang","orcid":"0000-0001-5549-3795","position":8,"is_corresponding":false},{"id":360785,"name":"Yongwei Zheng","orcid":"0000-0002-1947-5386","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T01:16:32.368674Z","pmid":"36961449","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":[]}