{"doi":"10.3389/fimmu.2021.705307","title":"Impaired B Cell Apoptosis Results in Autoimmunity That Is Alleviated by Ablation of Btk","abstract":"While apoptosis plays a role in B-cell self-tolerance, its significance in preventing autoimmunity remains unclear. Here, we report that dysregulated B cell apoptosis leads to delayed onset autoimmune phenotype in mice. Our longitudinal studies revealed that mice with B cell-specific deletion of pro-apoptotic Bim ( BBim fl/fl ) have an expanded B cell compartment with a notable increase in transitional, antibody secreting and recently described double negative (DN) B cells. They develop greater hypergammaglobulinemia than mice lacking Bim in all cells and accumulate several autoantibodies characteristic of Systemic Lupus Erythematosus (SLE) and related Sjögren’s Syndrome (SS) including anti-nuclear, anti-Ro/SSA and anti-La/SSB at a level comparable to NODH2h4 autoimmune mouse model. Furthermore, lymphocytes infiltrated the tissues including submandibular glands and formed follicle-like structures populated with B cells, plasma cells and T follicular helper cells indicative of ongoing immune reaction. This autoimmunity was ameliorated upon deletion of Bruton’s tyrosine kinase (Btk) gene, which encodes a key B cell signaling protein. These studies suggest that Bim-mediated apoptosis suppresses and B cell tyrosine kinase signaling promotes B cell-mediated autoimmunity.","journal":"Frontiers in Immunology","year":2021,"id":181457,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":732346,"name":"Cassandra Bazile","orcid":"0000-0002-3564-8806","position":1,"is_corresponding":false},{"id":733114,"name":"Emily S. Clark","orcid":null,"position":2,"is_corresponding":false},{"id":732347,"name":"Gianluca Carlesso","orcid":"0000-0002-9592-3267","position":3,"is_corresponding":false},{"id":732348,"name":"Justin C. Boucher","orcid":"0009-0008-8936-0470","position":4,"is_corresponding":false},{"id":733115,"name":"Eden Kleiman","orcid":null,"position":5,"is_corresponding":false},{"id":732349,"name":"Tamer I. Mahmoud","orcid":"0000-0001-7745-6178","position":6,"is_corresponding":false},{"id":732350,"name":"Lily Cheng","orcid":"0000-0002-3056-1891","position":7,"is_corresponding":false},{"id":732351,"name":"Darlah M. López-Rodríguez","orcid":"0000-0002-6002-4915","position":8,"is_corresponding":false},{"id":126594,"name":"Anne B. Satterthwaite","orcid":null,"position":9,"is_corresponding":false},{"id":733116,"name":"Norman H. Altman","orcid":null,"position":10,"is_corresponding":false},{"id":732352,"name":"Eric L. Greidinger","orcid":"0000-0003-3473-3846","position":11,"is_corresponding":false},{"id":732353,"name":"Wasif N. Khan","orcid":"0000-0002-7354-8312","position":12,"is_corresponding":false},{"id":733113,"name":"Jacqueline A. Wright","orcid":null,"position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-18T23:48:05.146883Z","pmid":"34512628","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":[]}