Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1241474/full |
| _version_ | 1797745123466936320 |
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| author | Elinor Wing Catherine Sutherland Katherine Miles David Gray Carl S. Goodyear Thomas D. Otto Stefan Breusch Graeme Cowan Mohini Gray |
| author_facet | Elinor Wing Catherine Sutherland Katherine Miles David Gray Carl S. Goodyear Thomas D. Otto Stefan Breusch Graeme Cowan Mohini Gray |
| author_sort | Elinor Wing |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T15:18:58Z |
| format | Article |
| id | doaj.art-7be81bbfafaa40f7b7970a61171c4912 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T15:18:58Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7be81bbfafaa40f7b7970a61171c49122023-08-11T06:07:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12414741241474Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritisElinor Wing0Catherine Sutherland1Katherine Miles2David Gray3Carl S. Goodyear4Thomas D. Otto5Stefan Breusch6Graeme Cowan7Mohini Gray8Centre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, The King’s Buildings, The University of Edinburgh, Edinburgh, United KingdomCentre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, The King’s Buildings, The University of Edinburgh, Edinburgh, United KingdomInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomInstitute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United KingdomOrthopaedic Unit, Royal Infirmary of Edinburgh, Edinburgh, United KingdomInstitute of Immunology and Infection Research, School of Biological Sciences, The King’s Buildings, The University of Edinburgh, Edinburgh, United KingdomCentre for Inflammation Research, The Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomB 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1241474/fullrheumatoid arthritisdouble-negative-2 (DN2) B cellsantibody secreting cellssynoviumsingle-cell sequencing |
| spellingShingle | Elinor Wing Catherine Sutherland Katherine Miles David Gray Carl S. Goodyear Thomas D. Otto Stefan Breusch Graeme Cowan Mohini Gray Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis Frontiers in Immunology rheumatoid arthritis double-negative-2 (DN2) B cells antibody secreting cells synovium single-cell sequencing |
| title | Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis |
| title_full | Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis |
| title_fullStr | Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis |
| title_full_unstemmed | Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis |
| title_short | Double-negative-2 B cells are the major synovial plasma cell precursor in rheumatoid arthritis |
| title_sort | double negative 2 b cells are the major synovial plasma cell precursor in rheumatoid arthritis |
| topic | rheumatoid arthritis double-negative-2 (DN2) B cells antibody secreting cells synovium single-cell sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1241474/full |
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