ArticleArthritis research & therapy2016
Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Trial
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Pathogenic Role of Cytokines in Rheumatoid Arthritis.Journal of clinical medicine · 2025Review
- The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis.International journal of molecular sciences · 2025Review
- Biological mechanisms of pulmonary inflammation and its association with seropositive rheumatoid arthritis.Frontiers in immunology · 2025Review
- A review of the pleiotropic actions of the IFN-inducible CXC chemokine receptor 3 ligands in the synovial microenvironment.Cellular and molecular life sciences : CMLS · 2023Review
- Review
- Immunomodulation Effect of Biomaterials on Bone Formation.Journal of functional biomaterials · 2022Review
- Mechanisms of joint destruction in rheumatoid arthritis - immune cell-fibroblast-bone interactions.Nature reviews. Rheumatology · 2022Review
- RANKL biology.Bone · 2022Review
- A CD40 variant is associated with systemic bone loss among patients with rheumatoid arthritis.Clinical rheumatology · 2022Article
- Toll-like receptor 9 deficiency induces osteoclastic bone loss via gut microbiota-associated systemic chronic inflammation.Bone research · 2022Article
- Personalized Therapeutic Strategies in the Management of Osteoporosis in Patients with Autoantibody-Positive Rheumatoid Arthritis.Journal of clinical medicine · 2022Review
- Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments.International journal of molecular sciences · 2022Review
- Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration.Bone research · 2022Review
- B Cells on the Stage of Inflammation in Juvenile Idiopathic Arthritis: Leading or Supporting Actors in Disease Pathogenesis?Frontiers in medicine · 2022Review
- The immune factors have complex causal regulation effects on bone mineral density.Frontiers in immunology · 2022Article
- Update on B Cell Response in Periodontitis.Advances in experimental medicine and biology · 2022Article
- The Neuroimmune Interplay in Joint Pain: The Role of Macrophages.Frontiers in immunology · 2022Review
- Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis.The Journal of clinical investigation · 2021Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation.
methodsPeripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells.
resultsRANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro.
conclusionsOur current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.
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