A comprehensive analysis of rheumatoid arthritis B cells reveals the importance of CD11c+ve double-negative-2 B cells as the major synovial plasma cell precursor.

Wing, E.; Sutherland, C.; Miles, K.; Gray, D.; Goodyear, C.; Otto, T. D.; Breusch, S.; Cowan, G. J. M.; Gray, M.

doi:10.1101/2023.02.15.526468

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bioRxiv · 10.1101/2023.02.15.526468

A comprehensive analysis of rheumatoid arthritis B cells reveals the importance of CD11c+ve double-negative-2 B cells as the major synovial plasma cell precursor.

Wing, E.·Sutherland, C.·Miles, K.·Gray, D.·Goodyear, C.·Otto, T. D.·Breusch, S.·Cowan, G. J. M.·Gray, M.

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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 targeted therapies. Here, we combine flow cytometry of circulating B cells with single-cell RNA and paired repertoire sequencing of over 27,000 synovial B cells from patients with established RA. Twelve B cell clusters were identified including previously recognised subsets, and a novel cluster that strongly expressed heat shock proteins. All lineages identified by trajectory analysis contribute to the DN2 B cell population, which is the major precursor to synovial ASCs. This was further supported by B cell receptor (BCR) lineage analysis, which revealed clonal relationships between DN2 cells and ASCs. This study advances our understanding of B cells in RA and reveals the origin of pathogenic ASCs in the RA synovium.

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Wing, E., Sutherland, C., Miles, K., Gray, D., Goodyear, C., Otto, T. D., Breusch, S., Cowan, G. J. M., Gray, M.. 2023-02-16. A comprehensive analysis of rheumatoid arthritis B cells reveals the importance of CD11c+ve double-negative-2 B cells as the major synovial plasma cell precursor.. https://doi.org/10.1101/2023.02.15.526468

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