Dynamic spectrum of ectopic lymphoid B cell activation and hypermutation in the RA synovium characterized by NR4A nuclear receptor expression.

Arthritis, Rheumatoid B-Lymphocytes Humans Plasma Cells / metabolism Receptors, Cytoplasmic and Nuclear / metabolism Synovial Membrane / metabolism
B cells CP: Immunology ectopic lymphoid structure rheumatoid arthritis single-cell RNA-seq synovial tissue

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
03 05 2022
Historique:
received: 13 09 2021
revised: 13 02 2022
accepted: 11 04 2022
entrez: 4 5 2022
pubmed: 5 5 2022
medline: 7 5 2022
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.celrep.2022.110766 PMID: 35508128 PMC: PMC9234997
pubmed: 35508128
pii: S2211-1247(22)00530-7
doi: 10.1016/j.celrep.2022.110766
pmc: PMC9234997
mid: NIHMS1808031
pii:
doi:

Substances chimiques

Receptors, Cytoplasmic and Nuclear 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

110766

Subventions

Organisme : NIAMS NIH HHS
ID : UH2 AR067685
Pays : United States
Organisme : NIAMS NIH HHS
ID : R21 AR071670
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002001
Pays : United States
Organisme : NIDCR NIH HHS
ID : R01 DE027245
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001866
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067681
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067688
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067689
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067690
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067677
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067694
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI078907
Pays : United States
Organisme : Medical Research Council
ID : G0800648
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : R01 AR078268
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067679
Pays : United States
Organisme : NIAMS NIH HHS
ID : UM2 AR067678
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR069655
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067676
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067691
Pays : United States

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests S.R. is a paid consultant for Gilead, Pfizer, Rheos, and J&J, and is a founder of Mestag. D.E.O. is an inventor of two non-licensed patents; US 63/031,861 entitled “markers and Cellular Antecedents of Rheumatoid Arthritis Flares” and US 63/050,155 entitled “method and System for RNA Isolation from Self-Collected and Small Volume Samples.” S.G. receives research support from Novartis and is a consultant for UCB.

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Auteurs

Nida Meednu (N)

Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.

Javier Rangel-Moreno (J)

Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.

Fan Zhang (F)

Center 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-Rivera (K)

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.

Elisa Corsiero (E)

Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.

Edoardo Prediletto (E)

Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.

Edward DiCarlo (E)

Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY 10021, USA.

Susan Goodman (S)

Hospital for Special Surgery, New York, NY 10021, USA; Weill Cornell Medicine, New York, NY, USA.

Laura T Donlin (LT)

Hospital for Special Surgery, New York, NY 10021, USA; Weill Cornell Medicine, New York, NY, USA.

Soumya Raychauduri (S)

Center 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 Bombardieri (M)

Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.

Costantino Pitzalis (C)

Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK.

Dana E Orange (DE)

Hospital for Special Surgery, New York, NY 10021, USA; Rockefeller University, New York, NY 10028, USA.

Andrew McDavid (A)

Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, USA.

Jennifer H Anolik (JH)

Division 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.

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Maladies auto-immunes › Polyarthrite rhumatoïde › Dynamic spectrum of ectopic lymphoid B cell...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › Dynamic spectrum of ectopic lymphoid B cell...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Dynamic spectrum of ectopic lymphoid B cell...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes B › Plasmocytes › Dynamic spectrum of ectopic lymphoid B cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Dynamic spectrum of ectopic lymphoid B cell...
questionsmedicales.fr › Appareil locomoteur › Squelette › Articulations › Capsule articulaire › Membrane synoviale › Dynamic spectrum of ectopic lymphoid B cell...