The Roles of B Cells and Their Interactions with Fibroblast-Like Synoviocytes in the Pathogenesis of Rheumatoid Arthritis

Wang, Qingtong; Ma, Yukun; Liu, Dandan; Zhang, Lingling; Wei, Wei

doi:10.1159/000321185

Cited by 33 publications

(19 citation statements)

References 121 publications

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“…Earlier studies described the relationship between B lymphocytes and RA-FLS interactions [88,89]. RA-FLSs act as ''nurse-like'' cells to B cells in the synovium through their expression of IL-6, BAFF, CXCL12 and vascular cell adhesion molecule-1 (VCAM-1), which helps mature B cell homing and survival.…”

Section: Fls Interacts With B and T Cellsmentioning

confidence: 99%

The role of BAFF in the progression of rheumatoid arthritis

2015

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Section: Fls Interacts With B and T Cellsmentioning

confidence: 99%

The role of BAFF in the progression of rheumatoid arthritis

2015

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“…Persistent synovial inflammation is one of the most characteristic features of RA, which leads to cartilage and bone destruction, and subsequent disability in RA [2-4]. The pathogenesis of RA is complex and encompasses many cell types, including T cells, B cells, monocytes/macrophages and fibroblast-like synoviocytes (FLSs); each has been proved to play distinct, complex and interrelated roles in the pathogenesis and progression of RA [5,6]. Our previous study found synovial infiltration with CD79a+ B cells, but not other B cell lineage, correlated with synovitis score and joint destruction in RA, which indicated synovial CD79a+ B cells may be a helpful biomarker for histologic disease activity and involved in the pathogenesis of joint destruction in RA [7].…”

Section: Introductionmentioning

confidence: 99%

Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovitis severity in rheumatoid arthritis

et al. 2012

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IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction and disability. Focal bone erosion is due to excess bone resorption of osteoclasts. Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the critical mediators both in inflammatory signal pathway and differentiation and resorption activity of osteoclasts. Here we aimed to investigate TRAF6 expression in RA synovium and its correlation with histological synovitis severity and radiological joint destruction in RA.MethodsSynovitis score was determined in needle biopsied synovium from 44 patients with active RA. Synovium from nine patients with osteoarthritis (OA) and seven with orthopedic arthropathies (Orth.A) were enrolled as "less inflamed" disease controls. Serial sections were stained immunohistochemically for TRAF6 as well as CD68 (macrophage), CD3 (T cell), CD20 (B cell), CD38 (plasmocyte), CD79a (B lineage cells from pre-B cell to plasmocyte stage), and CD34 (endothelial cell). Double immunofluorescence staining of TRAF6 and CD68 were tested. Densities of positive staining cells were determined and correlated with histological disease activity (synovitis score) and radiographic joint destruction (Sharp score).ResultsTRAF6 expression was found in the intimal and subintimal area of RA synovium, with intense staining found in the endochylema and nucleus of intimal synoviocytes and subintimal inflammatory cells. Double immunofluorescence staining showed TRAF6 was expressed in most of the intimal cells and obviously expressed in CD68+ cells and some other CD68- cells in subintimal area. Synovial TRAF6 was significantly over-expressed in the RA group compared with the OA and Orth.A group (2.53 ± 0.94 vs. 0.72 ± 0.44 and 0.71 ± 0.49, P < 0.0001). Synovial TRAF6 expression in RA correlated significantly with synovitis score (r = 0.412, P = 0.006), as well as the inflammatory cell infiltration (r = 0.367, P = 0.014). Significant correlation was detected between synovial TRAF6 expression and intimal CD68+ cells, as well as the cell density of subintimal CD68+ cells, CD3+ cells, CD20+ cells, CD38+ cells, and CD79a+ cells (all P < 0.05).ConclusionsElevated synovial TRAF6 expression correlated with synovitis severity and CD68+ cell density in RA. It is, therefore, hypothesized that synovial TRAF6 is involved in the pathogenesis of synovial inflammation and osteoclast differentiation in RA.

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“…Previously, we showed that DR2 expression was negatively related to disease activity, and other DRs have been correlated with acute phase reactants or clinical manifestations. B cells are one of the most important drivers of immunopathologies, and pathological findings also support that B cells could contribute to both the initiation and perpetuation of pathogenic immune responses in RA [19]. Reports of the efficacy of B cell depletion in RA patients revitalized interest in the pathogenic role of B cells in RA.…”

Section: Discussionmentioning

confidence: 99%

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis

Wei

Sun

Kong

et al. 2016

BMC Musculoskelet Disord

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BackgroundDopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA.MethodsPatients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence.ResultsThere were more DR2+CD19+ B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05).ConclusionThe frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2+CD19+ B cells in synovial tissues might have a role in bone metabolism and TNF-α production.

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The Roles of B Cells and Their Interactions with Fibroblast-Like Synoviocytes in the Pathogenesis of Rheumatoid Arthritis

Cited by 33 publications

References 121 publications

The role of BAFF in the progression of rheumatoid arthritis

The role of BAFF in the progression of rheumatoid arthritis

Upregulation of tumor necrosis factor receptor-associated factor 6 correlated with synovitis severity in rheumatoid arthritis

The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α levels in rheumatoid arthritis

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