{"doi":"10.1101/2023.03.18.533282","title":"Clonal associations of lymphocyte subsets and functional states revealed by single cell antigen receptor profiling of T and B cells in rheumatoid arthritis synovium","abstract":"Abstract Rheumatoid arthritis (RA) is an autoimmune disease initiated by antigen-specific T cells and B cells, which promote synovial inflammation through a complex set of interactions with innate immune and stromal cells. To better understand the phenotypes and clonal relationships of synovial T and B cells, we performed single-cell RNA and repertoire sequencing on paired synovial tissue and peripheral blood samples from 12 donors with seropositive RA ranging from early to chronic disease. Paired transcriptomic-repertoire analyses highlighted 3 clonally distinct CD4 T cells populations that were enriched in RA synovium: T peripheral helper (Tph) and T follicular helper (Tfh) cells, CCL5+ T cells, and T regulatory cells (Tregs). Among these cells, Tph cells showed a unique transcriptomic signature of recent T cell receptor (TCR) activation, and clonally expanded Tph cells expressed an elevated transcriptomic effector signature compared to non-expanded Tph cells. CD8 T cells showed higher oligoclonality than CD4 T cells, and the largest CD8 T cell clones in synovium were highly enriched in GZMK + cells. TCR analyses revealed CD8 T cells with likely viral-reactive TCRs distributed across transcriptomic clusters and definitively identified MAIT cells in synovium, which showed transcriptomic features of TCR activation. Among B cells, non-naive B cells including age-associated B cells (ABC), NR4A1+ activated B cells, and plasma cells, were enriched in synovium and had higher somatic hypermutation rates compared to blood B cells. Synovial B cells demonstrated substantial clonal expansion, with ABC, memory, and activated B cells clonally linked to synovial plasma cells. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate RA synovium.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390231,"datarank":0.5419941074763506,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.15725170385712006,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.15725170385712006,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":8,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":494315,"name":"Aaron B. Wagner","orcid":"0000-0001-9127-0089","position":1,"is_corresponding":false},{"id":226241,"name":"Nida Meednu","orcid":"0000-0002-2868-3339","position":2,"is_corresponding":false},{"id":226256,"name":"Fan Zhang","orcid":"0000-0002-6102-2970","position":3,"is_corresponding":false},{"id":226235,"name":"A. Helena Jonsson","orcid":"0000-0002-9558-2474","position":4,"is_corresponding":false},{"id":76150,"name":"Kevin Wei","orcid":"0000-0002-1821-167X","position":5,"is_corresponding":false},{"id":108713,"name":"Saori Sakaue","orcid":"0000-0003-3618-9717","position":6,"is_corresponding":false},{"id":291784,"name":"Aparna Nathan","orcid":"0000-0002-5975-2851","position":7,"is_corresponding":false},{"id":983892,"name":"Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network","orcid":null,"position":8,"is_corresponding":false},{"id":55631,"name":"Vivian P. Bykerk","orcid":"0000-0002-1219-3845","position":9,"is_corresponding":false},{"id":226219,"name":"Laura T. Donlin","orcid":"0000-0002-1428-090X","position":10,"is_corresponding":false},{"id":226230,"name":"Susan M. Goodman","orcid":"0000-0003-1197-7864","position":11,"is_corresponding":false},{"id":226228,"name":"Gary S. Firestein","orcid":"0000-0003-3495-960X","position":12,"is_corresponding":false},{"id":226224,"name":"David L. Boyle","orcid":"0000-0002-1454-2834","position":13,"is_corresponding":false},{"id":41942,"name":"V. Michael Holers","orcid":"0000-0002-5634-7746","position":14,"is_corresponding":false},{"id":27563,"name":"Larry W. Moreland","orcid":"0000-0003-4483-0359","position":15,"is_corresponding":false},{"id":229390,"name":"Darren Tabechian","orcid":null,"position":16,"is_corresponding":false},{"id":226247,"name":"Costantino Pitzalis","orcid":"0000-0003-1326-5051","position":17,"is_corresponding":false},{"id":226217,"name":"Andrew Filer","orcid":"0000-0001-8164-6249","position":18,"is_corresponding":false},{"id":35259,"name":"Soumya Raychaudhuri","orcid":"0000-0002-1901-8265","position":19,"is_corresponding":false},{"id":76152,"name":"Michael B. Brenner","orcid":"0000-0001-6202-8445","position":20,"is_corresponding":false},{"id":18044,"name":"Andrew McDavid","orcid":"0000-0002-6581-1213","position":21,"is_corresponding":false},{"id":226249,"name":"Deepak A. Rao","orcid":"0000-0001-9672-7746","position":22,"is_corresponding":false},{"id":226221,"name":"Jennifer H. Anolik","orcid":"0000-0002-1450-1549","position":23,"is_corresponding":false},{"id":854423,"name":"Garrett S. Dunlap","orcid":"0000-0002-2627-0506","position":0,"is_corresponding":true}],"reference_count":88,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:18:32.854511Z","pmid":"36993527","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":[]}