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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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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