{"doi":"10.1093/immhor/vlaf053","title":"Stage 1 type 1 diabetes memory B lymphocytes transcriptionally differ from healthy controls and harbor insulin-binding specificities","abstract":"Autoreactive B cell activity defines the earliest detectable stage (Stage 1) of type 1 diabetes (T1D) but is incompletely understood, particularly for B cells reactive against the key T1D autoantigen, insulin. To test whether Stage 1 T1D B cells are transcriptionally rewired compared to healthy individuals, we performed single-cell transcriptional, phenotypic, and immune repertoire profiling of CD19+ cells isolated from the peripheral blood of Stage 1 T1D individuals, identified via Type 1 Diabetes TrialNet as being positive for ≥ 2/5 islet autoantibodies, and healthy controls. Stage 1 T1D memory B cells upregulated n = 122 genes compared to healthy controls, including genes involved in actin cytoskeleton rearrangement, B cell receptor (BCR) signaling, and antigen presentation, and exhibited reduced BCR somatic hypermutation, particularly in atypical-like memory B cells. Clonally expanded B cells in the atypical-like memory subset of Stage 1 T1D individuals exhibited avidity driven insulin-binding specificities, without polyreactivity to HEp-2 cell autoantigens. Insulin-binding B cells showed non-significant upregulation of genes involved in key B cell functions. Our findings highlight transcriptional and BCR-repertoire differences in Stage 1 T1D B cells with potential for optimization as future screening tools to identify rare, autoreactive B cells and biomarkers of T1D progression.","journal":"ImmunoHorizons","year":2025,"id":548819,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9515,"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":290004,"name":"Wyatt J. McDonnell","orcid":"0000-0003-3859-2067","position":1,"is_corresponding":false},{"id":1442994,"name":"Christina T Brannon","orcid":null,"position":2,"is_corresponding":false},{"id":1442995,"name":"Nilesh P Kumar","orcid":null,"position":3,"is_corresponding":false},{"id":11900,"name":"S. Mallal","orcid":"0000-0002-7036-1309","position":4,"is_corresponding":false},{"id":290894,"name":"Ivelin S. Georgiev","orcid":"0000-0002-6312-7696","position":5,"is_corresponding":false},{"id":405167,"name":"James W. Thomas","orcid":"0000-0002-2098-6458","position":6,"is_corresponding":false},{"id":237705,"name":"Daniel J. Moore","orcid":"0000-0002-6889-9345","position":7,"is_corresponding":false},{"id":428126,"name":"Rachel H. Bonami","orcid":"0000-0001-7575-6943","position":8,"is_corresponding":false},{"id":993731,"name":"Lindsay E Bass","orcid":"0000-0002-3940-5633","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T02:54:03.053965Z","pmid":"41259806","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":[]}