{"doi":"10.1084/jem.20212553","title":"SARS-CoV-2 infection relaxes peripheral B cell tolerance","abstract":"Severe SARS-CoV-2 infection is associated with strong inflammation and autoantibody production against diverse self-antigens, suggesting a system-wide defect in B cell tolerance. BND cells are a B cell subset in healthy individuals harboring autoreactive but anergic B lymphocytes. In vitro evidence suggests inflammatory stimuli can breach peripheral B cell tolerance in this subset. We asked whether SARS-CoV-2-associated inflammation impairs BND cell peripheral tolerance. To address this, PBMCs and plasma were collected from healthy controls, individuals immunized against SARS-CoV-2, or subjects with convalescent or severe SARS-CoV-2 infection. We demonstrate that BND cells from severely infected individuals are significantly activated, display reduced inhibitory receptor expression, and restored BCR signaling, indicative of a breach in anergy during viral infection, supported by increased levels of autoreactive antibodies. The phenotypic and functional BND cell alterations significantly correlate with increased inflammation in severe SARS-CoV-2 infection. Thus, autoreactive BND cells are released from peripheral tolerance with SARS-CoV-2 infection, likely as a consequence of robust systemic inflammation.","journal":"The Journal of Experimental Medicine","year":2022,"id":248848,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":616172,"name":"Megan M. Stumpf","orcid":"0000-0001-8085-3094","position":1,"is_corresponding":false},{"id":888441,"name":"Nicholas R. Therrien","orcid":"0000-0001-5202-853X","position":2,"is_corresponding":false},{"id":497335,"name":"Mia J. Smith","orcid":"0000-0003-3042-5061","position":3,"is_corresponding":false},{"id":758889,"name":"Kelsey E. Lesteberg","orcid":"0000-0002-3081-457X","position":4,"is_corresponding":false},{"id":505201,"name":"Brent E. Palmer","orcid":"0000-0001-6932-065X","position":5,"is_corresponding":false},{"id":888442,"name":"James P. Maloney","orcid":"0000-0001-8348-4650","position":6,"is_corresponding":false},{"id":44871,"name":"William J. Janssen","orcid":"0000-0002-6397-3454","position":7,"is_corresponding":false},{"id":728388,"name":"Kara J. Mould","orcid":"0000-0003-2967-2778","position":8,"is_corresponding":false},{"id":571292,"name":"J. David Beckham","orcid":"0000-0001-9305-2683","position":9,"is_corresponding":false},{"id":489904,"name":"Roberta Pelanda","orcid":"0000-0001-8941-3941","position":10,"is_corresponding":false},{"id":351700,"name":"Raul M. Torres","orcid":"0000-0002-5969-5957","position":11,"is_corresponding":false},{"id":888440,"name":"Moriah J. Castleman","orcid":"0000-0001-7219-5044","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:14.794521Z","pmid":"35420627","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":[]}