{"doi":"10.1016/j.celrep.2025.115425","title":"Activated polyreactive B cells are clonally expanded in autoantibody positive and patients with recent-onset type 1 diabetes","abstract":"Autoreactive B cells play an important but ill-defined role in autoimmune type 1 diabetes (T1D). We isolated pancreatic islet antigen-reactive B cells from the peripheral blood of non-diabetic autoantibody-negative first-degree relatives, autoantibody-positive, and recent-onset T1D donors. Single-cell RNA sequencing analysis revealed that islet antigen-reactive B cells from autoantibody-positive and T1D donors had altered gene expression in pathways associated with B cell signaling and inflammation. Additionally, BCR sequencing uncovered a similar shift in islet antigen-reactive B cell repertoires among autoantibody-positive and T1D donors where greater clonal expansion was also observed. Notably, a substantial fraction of islet antigen-reactive B cells in autoantibody-positive and T1D donors appeared to be polyreactive, which was corroborated by analysis of recombinant monoclonal antibodies. These results expand our understanding of autoreactive B cell phenotypes during T1D and identify unique BCR repertoire changes that may serve as biomarkers for increased disease risk.","journal":"Cell Reports","year":2025,"id":518075,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9518,"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":1383261,"name":"Fatima Tensun","orcid":null,"position":1,"is_corresponding":false},{"id":1385499,"name":"Spencer A. Evans","orcid":null,"position":2,"is_corresponding":false},{"id":1057531,"name":"Kevin P. Toole","orcid":"0009-0003-2694-5141","position":3,"is_corresponding":false},{"id":867108,"name":"Jessica E. Lee","orcid":"0000-0002-5626-4297","position":4,"is_corresponding":false},{"id":764242,"name":"Hali Broncucia","orcid":"0000-0003-2056-2169","position":5,"is_corresponding":false},{"id":87044,"name":"Jay R. Hesselberth","orcid":"0000-0002-6299-179X","position":6,"is_corresponding":false},{"id":336608,"name":"Peter A. Gottlieb","orcid":"0000-0002-7601-8536","position":7,"is_corresponding":false},{"id":282722,"name":"Kristen L. Wells","orcid":"0000-0002-7466-8164","position":8,"is_corresponding":false},{"id":497335,"name":"Mia J. Smith","orcid":"0000-0003-3042-5061","position":9,"is_corresponding":false},{"id":1057529,"name":"Catherine A. Nicholas","orcid":"0000-0003-2724-266X","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:49:04.756302Z","pmid":"40117290","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":[]}