Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis

Elinor Wing, Catherine Sutherland, Katherine Miles, David Gray, Carl S Goodyear, Thomas D. Otto, Stefan Breusch, Graeme Cowan, Mohini Gray

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

B cells are key pathogenic drivers of chronic inflammation in rheumatoid arthritis(RA). There is limited understanding of the relationship between synovial B cell subsets and pathogenic antibody secreting cells (ASCs). This knowledge is crucial for the development of more targeted B-cell depleting therapies. While CD11c+ double-negative 2 (DN2) B cells have been suggested as an ASC precursor in lupus, to date there is no proven link between the two subsets in RA. We have used both single-cell gene expression and BCR sequencing to study synovial B cells from patients with established RA, in addition to flow cytometry of circulating B cells. To better understand the differentiation patterns within the diseased tissue, a combination of RNA-based trajectory inference and clonal lineage analysis of BCR relationships were used. Both forms of analysis indicated that DN2 B cells serve as a major precursors to synovial ASCs. This study advances our understanding of B cells in RA and reveals the origin of pathogenic ASCs in the RA synovium. Given the significant role of DN2 B cells as a progenitor to pathogenic B cells in RA, it is important to conduct additional research to investigate the origins of DN2 B cells in RA and explore their potential as therapeutic targets in place of the less specific panB cells depletion therapies currently in use.
Original languageEnglish
Number of pages14
JournalFrontiers in Immunology
Publication statusPublished - 10 Aug 2023

Keywords / Materials (for Non-textual outputs)

  • rheumatoid arthritis
  • double-negative-2 (DN2) B cells
  • antibody secreting cells
  • synovium
  • single-cell sequencing


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