{"doi":"10.1172/jci189074","title":"CTLA-4 blockade shifts the B cell repertoire toward autoimmunity","abstract":"Checkpoint inhibitors targeting CTLA-4 and PD-1 revolutionized the treatment of cancer patients, but their use is limited by the emergence of immune-related adverse events (irAEs). We assessed autoreactive B cell frequencies in the blood of cancer patients before and after treatment with checkpoint inhibitors by testing the reactivity of recombinant antibodies cloned from single B cells. We found that anti-PD-1 and anti-CTLA-4 combination therapy induced the emergence of autoreactive mature naive B cells, whereas central B cell tolerance remained functional. In contrast, anti-PD-1 alone did not alter autoreactive B cell counterselection. Anti-CTLA-4 injections in humanized mice also resulted in the production of autoreactive B cells, whereas anti-PD-1 did not. We conclude that CTLA-4 but not PD-1 is required for the removal of developing autoreactive mature naive B cells and that CTLA-4 blockade broadens the peripheral B cell repertoire, which likely contains clones that promote not only irAEs but also antitumor responses.","journal":"Journal of Clinical Investigation","year":2025,"id":524563,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":323573,"name":"Meng Wang","orcid":"0000-0002-3453-7805","position":1,"is_corresponding":false},{"id":107008,"name":"Yile Dai","orcid":"0000-0002-7761-3361","position":2,"is_corresponding":false},{"id":1398082,"name":"Adrien Mirouse","orcid":"0000-0002-5755-8043","position":3,"is_corresponding":false},{"id":1398610,"name":"Clarence Rachel Villanueva-Pachas","orcid":null,"position":4,"is_corresponding":false},{"id":700765,"name":"Delphine Bouis","orcid":"0000-0002-4917-3135","position":5,"is_corresponding":false},{"id":700768,"name":"Joshua M. Boeckers","orcid":"0000-0002-3314-4743","position":6,"is_corresponding":false},{"id":700767,"name":"Ruchi Gera","orcid":"0000-0002-7043-4096","position":7,"is_corresponding":false},{"id":1398611,"name":"Sally Yraita","orcid":null,"position":8,"is_corresponding":false},{"id":1398612,"name":"L.M. de la Escalera Clapp","orcid":null,"position":9,"is_corresponding":false},{"id":571209,"name":"Ana Luisa Perdigoto","orcid":"0000-0002-0348-9329","position":10,"is_corresponding":false},{"id":701418,"name":"Fabien Delmotte","orcid":null,"position":11,"is_corresponding":false},{"id":719208,"name":"Christopher Massad","orcid":"0000-0002-4786-4880","position":12,"is_corresponding":false},{"id":110536,"name":"Antonietta Bacchiocchi","orcid":null,"position":13,"is_corresponding":false},{"id":17340,"name":"Aaron M. Ring","orcid":"0000-0003-3699-2446","position":14,"is_corresponding":false},{"id":69468,"name":"Yuval Kluger","orcid":"0000-0002-3035-071X","position":15,"is_corresponding":false},{"id":226323,"name":"Harriet M. Kluger","orcid":"0000-0002-4932-9873","position":16,"is_corresponding":false},{"id":230352,"name":"Kevan C. Herold","orcid":"0000-0003-1534-6613","position":17,"is_corresponding":false},{"id":395328,"name":"Eric Meffre","orcid":"0000-0003-4326-0171","position":18,"is_corresponding":false},{"id":395323,"name":"Elif Çakan","orcid":"0000-0002-5606-2070","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:50:12.083054Z","pmid":"41026527","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":[]}