Dysregulated B cell function and disease pathogenesis in systemic sclerosis
Systemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.999008/full |
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| author | Claire F. Beesley Nina R. Goldman Taher E. Taher Christopher P. Denton David J. Abraham Rizgar A. Mageed Voon H. Ong |
| author_facet | Claire F. Beesley Nina R. Goldman Taher E. Taher Christopher P. Denton David J. Abraham Rizgar A. Mageed Voon H. Ong |
| author_sort | Claire F. Beesley |
| collection | DOAJ |
| description | Systemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined clinically relevant autoantibodies indicates that B cells play a fundamental role in the pathogenesis and development of SSc. This is supported by B cell and fibroblast coculture experiments revealing that B cells directly enhance collagen and extracellular matrix synthesis in fibroblasts. In addition, B cells from SSc patients produce large amounts of profibrotic cytokines such as IL-6 and TGF-β, which interact with other immune and endothelial cells, promoting the profibrotic loop. Furthermore, total B cell counts are increased in SSc patients compared with healthy donors and specific differences can be found in the content of naïve, memory, transitional and regulatory B cell compartments. B cells from SSc patients also show differential expression of activation markers such as CD19 which may shape interactions with other immune mediators such as T follicular helper cells and dendritic cells. The key role of B cells in SSc is further supported by the therapeutic benefit of B cell depletion with rituximab in some patients. It is notable also that B cell signaling is impaired in SSc patients, and this could underpin the failure to induce tolerance in B cells as has been shown in murine models of scleroderma. |
| first_indexed | 2024-04-10T22:40:59Z |
| format | Article |
| id | doaj.art-c03e3cb5b4e74408a4563c6c8163b069 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T22:40:59Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c03e3cb5b4e74408a4563c6c8163b0692023-01-16T05:34:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.999008999008Dysregulated B cell function and disease pathogenesis in systemic sclerosisClaire F. Beesley0Nina R. Goldman1Taher E. Taher2Christopher P. Denton3David J. Abraham4Rizgar A. Mageed5Voon H. Ong6Centre for Rheumatology, Division of Medicine, University College London, London, United KingdomCentre for Rheumatology, Division of Medicine, University College London, London, United KingdomInstitute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United KingdomCentre for Rheumatology, Division of Medicine, University College London, London, United KingdomCentre for Rheumatology, Division of Medicine, University College London, London, United KingdomCentre for Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, United KingdomCentre for Rheumatology, Division of Medicine, University College London, London, United KingdomSystemic sclerosis (SSc) is a complex, immune-mediated rheumatic disease characterised by excessive extracellular matrix deposition in the skin and internal organs. B cell infiltration into lesional sites such as the alveolar interstitium and small blood vessels, alongside the production of defined clinically relevant autoantibodies indicates that B cells play a fundamental role in the pathogenesis and development of SSc. This is supported by B cell and fibroblast coculture experiments revealing that B cells directly enhance collagen and extracellular matrix synthesis in fibroblasts. In addition, B cells from SSc patients produce large amounts of profibrotic cytokines such as IL-6 and TGF-β, which interact with other immune and endothelial cells, promoting the profibrotic loop. Furthermore, total B cell counts are increased in SSc patients compared with healthy donors and specific differences can be found in the content of naïve, memory, transitional and regulatory B cell compartments. B cells from SSc patients also show differential expression of activation markers such as CD19 which may shape interactions with other immune mediators such as T follicular helper cells and dendritic cells. The key role of B cells in SSc is further supported by the therapeutic benefit of B cell depletion with rituximab in some patients. It is notable also that B cell signaling is impaired in SSc patients, and this could underpin the failure to induce tolerance in B cells as has been shown in murine models of scleroderma.https://www.frontiersin.org/articles/10.3389/fimmu.2022.999008/fullautoantibodiessystemic sclerosis (scleroderma)autoimmunityB cellsfibrosis |
| spellingShingle | Claire F. Beesley Nina R. Goldman Taher E. Taher Christopher P. Denton David J. Abraham Rizgar A. Mageed Voon H. Ong Dysregulated B cell function and disease pathogenesis in systemic sclerosis Frontiers in Immunology autoantibodies systemic sclerosis (scleroderma) autoimmunity B cells fibrosis |
| title | Dysregulated B cell function and disease pathogenesis in systemic sclerosis |
| title_full | Dysregulated B cell function and disease pathogenesis in systemic sclerosis |
| title_fullStr | Dysregulated B cell function and disease pathogenesis in systemic sclerosis |
| title_full_unstemmed | Dysregulated B cell function and disease pathogenesis in systemic sclerosis |
| title_short | Dysregulated B cell function and disease pathogenesis in systemic sclerosis |
| title_sort | dysregulated b cell function and disease pathogenesis in systemic sclerosis |
| topic | autoantibodies systemic sclerosis (scleroderma) autoimmunity B cells fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.999008/full |
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