ArticleCell reports2022
Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26 citing papers in PubMed, 38 citations in OpenAlex.
- Immune-mediated rheumatoid arthritis: from single-cell genomics to new therapies.Nature immunology · 2026Review
- Tumor-infiltrating B cells evolve towards interferon-rich trajectories aligned with immunotherapy in melanoma.Journal of experimental & clinical cancer research : CR · 2026Article
- CXCL13⁺ CD4⁺ T cells are associated with B-cell recruitment and lesion progression in cerebral cavernous malformations.Journal of neuroinflammation · 2026Article
- [Rheumatoid arthritis-more than just a joint disease : Overview for internal medicine practice].Innere Medizin (Heidelberg, Germany) · 2026Review
- Longitudinal clinical proteomics reveals pneumonia type-specific protein biomarkers and autoantibodies.JCI insight · 2026Article
- Inflammation-Driven Lymphoid Structures: Organization, Function, and Clinical Impact Across Autoimmunity, Cancer, and Checkpoint Toxicity.Immunological reviews · 2026Review
- Roads and detours for CAR T cell therapy in autoimmune diseases.Nature reviews. Drug discovery · 2026Review
- Longitudinal clinical proteomics reveals pneumonia type-specific protein biomarkers and autoantibodies.medRxiv : the preprint server for health sciences · 2026Article
- Revisiting B-cell targeted therapies in rheumatoid arthritis: from paradoxical biology to deep immune reset.Frontiers in immunology · 2026Review
- Augmentation of PRDX1-DOK3 interaction alleviates rheumatoid arthritis progression by suppressing plasma cell differentiation.Acta pharmaceutica Sinica. B · 2025Article
- Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis.The Journal of clinical investigation · 2025Article
- Single-cell transcriptomics of melanoma sentinel lymph nodes identifies immune cell signatures associated with metastasis.JCI insight · 2025Article
- Deep topic modeling of spatial transcriptomics in the rheumatoid arthritis synovium identifies distinct classes of ectopic lymphoid structures.bioRxiv : the preprint server for biology · 2025Article
- Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.Nature communications · 2024Article
- The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis.Nature communications · 2024Article
- Advancing skeletal health and disease research with single-cell RNA sequencing.Military Medical Research · 2024Review
- Synovial Tissue Insights into Heterogeneity of Rheumatoid Arthritis.Current rheumatology reports · 2024Review
- Review
- Computer Vision Analysis of Rheumatoid Arthritis Synovium Reveals Lymphocytic Inflammation Is Associated With Immunoglobulin Skewing in Blood.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Matrix metalloproteinases in arthritis: towards precision medicine.Nature reviews. Rheumatology · 2023Review
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Authors and funding
16 authors at 5 institutions in 2 countries.
Nida MeednuDivision of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Javier Rangel-MorenoDivision of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Fan ZhangCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA 02115, USA.
Katherine Escalera-RiveraDepartment of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA.
Elisa CorsieroCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.
Edoardo PredilettoCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.
Edward DiCarloDepartment of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY 10021, USA.
Susan GoodmanHospital for Special Surgery, New York, NY 10021, USA; Weill Cornell Medicine, New York, NY, USA.
Laura T DonlinHospital for Special Surgery, New York, NY 10021, USA; Weill Cornell Medicine, New York, NY, USA.
Soumya RaychauduriCenter for Data Sciences, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142, USA; Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA 02115, USA; Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
Michele BombardieriCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.
Costantino PitzalisCentre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.
Dana E OrangeHospital for Special Surgery, New York, NY 10021, USA; Rockefeller University, New York, NY 10028, USA.
Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium
Andrew McDavidDepartment of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, USA.
Jennifer H AnolikDivision of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA; Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA; Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA. Electronic address: jennifer_anolik@urmc.rochester.edu.
Hospital for Special Surgery · USQueen Mary University of London · GBUniversity of Rochester Medical Center · USBroad Institute · USUniversity of Rochester · US
Funding
Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6MThe University of Rochester's Clinical and Translational Science InstituteUL1TR002001 · NCATS · UNIVERSITY OF ROCHESTER · PI WILSON, KAREN M., ZAND, MARTIN S · 2016 to 2024
$34.6MRole of B Cells in Synovial Inflammation & LN Remodeling in RA ArthritisP01AI078907 · NIAID · UNIVERSITY OF ROCHESTER · PI ANOLIK, JENNIFER HOWITT · 2010 to 2014
$10.8MPEARL: Pathway Exploration and Analysis in Renal LupusUH2AR067688 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI DIAMOND, BETTY, WOFSY, DAVID · 2014 to 2020
$9.0MTissue Acquisition Research GroupUM2AR067678 · NIAMS · STANFORD UNIVERSITY · PI HOLERS, VERNON MICHAEL, UTZ, PAUL JOSEPH · 2014 to 2020
$8.2MRochester Resource-Based Center for Bone, Muscle and Orthopaedic Research (ROCSTARR) (Overall Application)P30AR069655 · NIAMS · UNIVERSITY OF ROCHESTER · PI Edward M. Schwarz · 2016 to 2026
$7.8MMulti-Ethnic Translational Research Optimization (METRO) Lupus ConsortiumUH2AR067689 · NIAMS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BUYON, JILL P, PUTTERMAN, CHAIM · 2014 to 2020
$6.3MEvolving Adaptive and Effector Mechanisms from Pre-RA Through Established DiseaseUH2AR067681 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 2014 to 2020
$5.5MMolecular and Cellular Dissection of Early Rheumatoid ArthritisUH2AR067694 · NIAMS · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI BRENNER, MICHAEL B., GREGERSEN, PETER K. · 2014 to 2020
$5.4MRA-SLE Molecular Deconstruction Leadership CenterUH2AR067677 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI BRENNER, MICHAEL B., RAYCHAUDHURI, SOUMYA · 2014 to 2020
$4.3MTargeting tonsillar B cells for the induction of effective mucosal immunity to HIVR01DE027245 · NIDCR · UNIVERSITY OF ROCHESTER · PI KOBIE, JAMES J · 2017 to 2021
$3.7MInvestigating Mucosal Breaks in the Initiation and Progression of Rheumatoid ArthritisR01AR078268 · NIAMS · STANFORD UNIVERSITY · PI ORANGE, DANA ELIZABETH, ROBINSON, WILLIAM H · 2021 to 2025
$3.1MMedical Research Council G0800648NCATS NIH HHS UL1 TR001866NCATS NIH HHS UL1 TR002001NIAID NIH HHS P01 AI078907NIAMS NIH HHS P30 AR069655NIAMS NIH HHS R01 AR078268NIAMS NIH HHS R21 AR071670NIAMS NIH HHS UH2 AR067676NIAMS NIH HHS UH2 AR067677NIAMS NIH HHS UH2 AR067679NIAMS NIH HHS UH2 AR067681NIAMS NIH HHS UH2 AR067685NIAMS NIH HHS UH2 AR067688NIAMS NIH HHS UH2 AR067689NIAMS NIH HHS UH2 AR067690NIAMS NIH HHS UH2 AR067691NIAMS NIH HHS UH2 AR067694NIAMS NIH HHS UM2 AR067678NIDCR NIH HHS R01 DE027245
Abstract
Ectopic lymphoid structures (ELS) can develop in rheumatoid arthritis (RA) synovial tissue, but the precise pathways of B cell activation and selection are not well understood. Here, we identify a synovial B cell population characterized by co-expression of a family of orphan nuclear receptors (NR4A1-3), which is highly enriched in RA synovial tissue. A transcriptomic profile of NR4A synovial B cells significantly overlaps with germinal center light zone B cells and an accrual of somatic hypermutation that correlates with loss of naive B cell state. NR4A B cells co-express lymphotoxins α and β and IL-6, supporting functions in ELS promotion. Expanded and shared clones between synovial NR4A B cells and plasma cells and the rapid upregulation with BCR stimulation point to in situ differentiation. Together, we identify a dynamic progression of B cell activation in RA synovial ELS, with NR4A transcription factors having an important role in local adaptive immune responses.
Indexed as
Arthritis, RheumatoidSynovial MembraneB-LymphocytesHumansPlasma CellsReceptors, Cytoplasmic and NuclearReceptors, Cytoplasmic and NuclearB cellsCP: Immunologyectopic lymphoid structurerheumatoid arthritissingle-cell RNA-seqsynovial tissue
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