{"doi":"10.1172/jci150985","title":"Positive and negative selection shape the human naive B cell repertoire","abstract":"Although negative selection of developing B cells in the periphery is well described, yet poorly understood, evidence of naive B cell positive selection remains elusive. Using 2 humanized mouse models, we demonstrate that there was strong skewing of the expressed immunoglobulin repertoire upon transit into the peripheral naive B cell pool. This positive selection of expanded naive B cells in humanized mice resembled that observed in healthy human donors and was independent of autologous thymic tissue. In contrast, negative selection of autoreactive B cells required thymus-derived Tregs and MHC class II-restricted self-antigen presentation by B cells. Indeed, both defective MHC class II expression on B cells of patients with rare bare lymphocyte syndrome and prevention of self-antigen presentation via HLA-DM inhibition in humanized mice resulted in the production of autoreactive naive B cells. These latter observations suggest that Tregs repressed autoreactive naive B cells continuously produced by the bone marrow. Thus, a model emerged, in which both positive and negative selection shaped the human naive B cell repertoire and that each process was mediated by fundamentally different molecular and cellular mechanisms.","journal":"Journal of Clinical Investigation","year":2021,"id":169647,"datarank":0.9960366103499407,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.48585700310061725,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.48585700310061725,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":27,"citers_with_citation_signal":25,"citers_with_endowment":25,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.955,"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":700762,"name":"Jean-Nicolas Schickel","orcid":"0009-0002-0592-8150","position":1,"is_corresponding":false},{"id":700763,"name":"Nikolaos Tsakiris","orcid":"0000-0001-6821-6850","position":2,"is_corresponding":false},{"id":700764,"name":"Joel Sng","orcid":"0000-0002-5623-8873","position":3,"is_corresponding":false},{"id":701417,"name":"Florent Arbogast","orcid":null,"position":4,"is_corresponding":false},{"id":700765,"name":"Delphine Bouis","orcid":"0000-0002-4917-3135","position":5,"is_corresponding":false},{"id":700766,"name":"Daniele Parisi","orcid":"0000-0002-2497-7487","position":6,"is_corresponding":false},{"id":700767,"name":"Ruchi Gera","orcid":"0000-0002-7043-4096","position":7,"is_corresponding":false},{"id":700768,"name":"Joshua M. Boeckers","orcid":"0000-0002-3314-4743","position":8,"is_corresponding":false},{"id":701418,"name":"Fabien Delmotte","orcid":null,"position":9,"is_corresponding":false},{"id":274503,"name":"Margaret Veselits","orcid":"0000-0001-8755-6260","position":10,"is_corresponding":false},{"id":490851,"name":"Catharina Schuetz","orcid":"0000-0001-8731-8924","position":11,"is_corresponding":false},{"id":517472,"name":"Eva‐Maria Jacobsen","orcid":"0000-0003-4750-0136","position":12,"is_corresponding":false},{"id":700769,"name":"Carsten Posovszky","orcid":"0000-0002-9487-8812","position":13,"is_corresponding":false},{"id":490855,"name":"Ansgar Schulz","orcid":"0000-0002-7798-7996","position":14,"is_corresponding":false},{"id":700770,"name":"Klaus Schwarz","orcid":"0000-0001-5455-2394","position":15,"is_corresponding":false},{"id":262502,"name":"Marcus R. Clark","orcid":"0000-0003-4747-0387","position":16,"is_corresponding":false},{"id":700771,"name":"Laurence Ménard","orcid":"0000-0003-2093-0734","position":17,"is_corresponding":false},{"id":395328,"name":"Eric Meffre","orcid":"0000-0003-4326-0171","position":18,"is_corresponding":false},{"id":700761,"name":"Jeff W. Chen","orcid":"0000-0002-3371-7820","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:46:15.560174Z","pmid":"34813502","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":[]}