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 panB cells depletion therapies currently in use.
Original language | English |
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Number of pages | 14 |
Journal | Frontiers in Immunology |
Volume | 14 |
DOIs | |
Publication status | Published - 10 Aug 2023 |
Keywords / Materials (for Non-textual outputs)
- rheumatoid arthritis
- double-negative-2 (DN2) B cells
- antibody secreting cells
- synovium
- single-cell sequencing