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

Nida Meednu; Javier Rangel-Moreno; Fan Zhang; Katherine Escalera-Rivera; Elisa Corsiero; Edoardo Prediletto; Edward DiCarlo; Susan Goodman; Laura T. Donlin; Soumya Raychauduri; Michele Bombardieri; Costantino Pitzalis; Dana E. Orange; Andrew McDavid; Jennifer H. Anolik

Cell Reports (May 2022)

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

Nida Meednu,
Javier Rangel-Moreno,
Fan Zhang,
Katherine Escalera-Rivera,
Elisa Corsiero,
Edoardo Prediletto,
Edward DiCarlo,
Susan Goodman,
Laura T. Donlin,
Soumya Raychauduri,
Michele Bombardieri,
Costantino Pitzalis,
Dana E. Orange,
Andrew McDavid,
Jennifer H. Anolik

Affiliations

Nida Meednu: Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Javier Rangel-Moreno: Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Fan Zhang: 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: 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: Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK
Edoardo Prediletto: Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK
Edward DiCarlo: Department of Pathology and Laboratory Medicine, Hospital for Special Surgery, New York, NY 10021, USA
Susan Goodman: Hospital for Special Surgery, New York, NY 10021, USA; Weill Cornell Medicine, New York, NY, USA
Laura T. Donlin: Hospital for Special Surgery, New York, NY 10021, USA; Weill Cornell Medicine, New York, NY, USA
Soumya Raychauduri: 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: Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK
Costantino Pitzalis: Centre for Experimental Medicine & Rheumatology, William Harvey Research Institute, Queen Mary University of London, EC1M 6BQ, London, UK
Dana E. Orange: Hospital for Special Surgery, New York, NY 10021, USA; Rockefeller University, New York, NY 10028, USA
Andrew McDavid: Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY 14642, USA
Jennifer H. Anolik: 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; Corresponding author

Journal volume & issue: Vol. 39, no. 5
p. 110766

Abstract

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Summary: 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.

CP: Immunology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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