ArticleAnnals of the rheumatic diseases2015
Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis.
Article in Annals of the rheumatic diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
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Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Intraepithelial lymphocytes in human oral diseases.Frontiers in immunology · 2025Pooled it
- Effects of the anti-RANKL antibody denosumab on joint structural damage in patients with rheumatoid arthritis treated with conventional synthetic disease-modifying antirheumatic drugs (DESIRABLE study): a randomised, double-blind, placebo-controlled phase 3 trial.Annals of the rheumatic diseases · 2019Trial
- Human CD21Journal of human immunity · 2026Review
- Mechanisms of osteoclast activation in inflammatory bone loss in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis.International journal of molecular sciences · 2025Review
- B cells in non-lymphoid tissues.Nature reviews. Immunology · 2025Review
- Early multiple sclerosis activity associated with TBX21+CD21loCXCR3+ B cell expansion resembling EBV-induced phenotypes.JCI insight · 2025Article
- FCRLs and atypical transcriptional pattern in tumor infiltrating B cells from lung and renal cancer.Frontiers in immunology · 2025Article
- The Increased FCRL mRNA Expression in Patients with Graves' Disease Is Associated with Hyperthyroidism (But Not with Positive Thyroid Antibodies).Journal of clinical medicine · 2024Article
- Dynamic changes in B cell subpopulations in response to triple-negative breast cancer development.Scientific reports · 2024Article
- Gut-associated lymphoid tissue: a microbiota-driven hub of B cell immunity.Trends in immunology · 2024Review
- Cartilage destruction in early rheumatoid arthritis patients correlates with CD21Arthritis research & therapy · 2024Article
- Exploring the therapeutic opportunities of potassium channels for the treatment of rheumatoid arthritis.Frontiers in pharmacology · 2024Review
- Cross-disorder genetic analysis of immune diseases reveals distinct gene associations that converge on common pathways.Nature communications · 2023Article
- Characterization of age-associated B cells in early drug-naïve rheumatoid arthritis patients.Immunology · 2023Article
- Tumor microenvironment remodeling after neoadjuvant immunotherapy in non-small cell lung cancer revealed by single-cell RNA sequencing.Genome medicine · 2023Article
- Review
- Identification of biomarkers in patients with rheumatoid arthritis responsive to DMARDs but with progressive bone erosion.Frontiers in immunology · 2023Article
- B cells in human lymphoid structures.Clinical and experimental immunology · 2022Review
- Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
objectivesThe success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium.
methodsSynovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4(+) and FcRL4(-) B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR.
resultsRANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4- B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA.
conclusionsWe have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug.
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