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

Wing, E., Sutherland, C., Miles, K., Gray, D., Goodyear, C. S. , Otto, T. D. , Breusch, S., Cowan, G. and Gray, M. (2023) Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis. Frontiers in Immunology, 14, 1241474. (doi: 10.3389/fimmu.2023.1241474) (PMID:37638026) (PMCID:PMC10450142)

Abstract

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 pan-B cells depletion therapies currently in use.

• Item Type: Articles
• Additional Information: This work was supported by grants from the Medical Research Council (MR/N013166/1) to MG and EW, the Wellcome Trust (220096/Z/20/Z) to CS, and CSO (TCS/22/03) to MG.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas and Goodyear, Professor Carl
• Authors: Wing, E., Sutherland, C., Miles, K., Gray, D., Goodyear, C. S., Otto, T. D., Breusch, S., Cowan, G., and Gray, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Frontiers in Immunology
• Publisher: Frontiers Media
• ISSN: 1664-3224
• ISSN (Online): 1664-3224
• Copyright Holders: Copyright © 2023 Wing, Sutherland, Miles, Gray, Goodyear, Otto, Breusch, Cowan and Gra
• First Published: First published in Frontiers in Immunology 14:1241474
• Publisher Policy: Reproduced under a Creative Commons license