Chemokine receptor expression and functional effects of chemokines on B cells: implication in the pathogenesis of rheumatoid arthritis.
Chemokine receptor expression and functional effects of chemokines on B cells: implication in the pathogenesis of rheumatoid arthritis.
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DOI：
10.1186/ar2823
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发表时间：
2009
影响因子：
4.9
通讯作者：
Miyasaka N
中科院分区：
文献类型：
--
作者：
Nanki T;Takada K;Komano Y;Morio T;Kanegane H;Nakajima A;Lipsky PE;Miyasaka N
B细胞在类风湿性关节炎（RA）滑膜中的积累已有报道，并且认为这些细胞可能通过抗原呈递、自身抗体产生和/或炎性细胞因子产生而促成RA的发病。趋化因子可促进B细胞在滑膜中的聚集。本研究的目的是确定趋化因子受体表达的B细胞在外周血中的正常捐助者和受试者与RA，在炎症部位的RA，和趋化因子对B细胞活化的影响。流式细胞术分析细胞表面分子表达。使用趋化性室评估细胞迁移。3 H-胸腺嘧啶核苷掺入法检测细胞增殖。用酶联免疫吸附法测定肿瘤坏死因子（TNF）的产生。健康供者和RA受试者的外周血B细胞表达CC趋化因子受体（CCR）5和CXCR 3，大多数B细胞表达CCR 6、CCR 7、CXCR 4和CXCR 5。健康人和RA患者外周血B细胞中CCR 5的表达频率高于CD 27-B细胞。与外周血相比，RA患者滑膜B细胞更频繁地表达CCR 5，但较少表达CCR 6、CCR 7和CXCR 5。对来自健康供体的外周血B细胞进行进一步的功能分析。CC趋化因子配体（CCL）20、CCL 19、CCL 21和CXCL 12可增强外周血B细胞，尤其是CD 27 + B细胞的迁移。所有四种趋化因子单独诱导B细胞增殖;其中CCL 21最有效。CCL 21还增强抗免疫球蛋白（IG）M刺激的B细胞的增殖，并且阻断CCR 7抑制这种作用。CCL 20、CCL 21和CXCL 12增强抗IgM mAb刺激的B细胞产生TNF。最后，刺激与CXCL 12，而不是CCL 20，CCL 19和CCL 21，增强诱导型共刺激因子配体（ICOSL）的表达由外周血B细胞的健康供体和RA，但不增加B细胞活化因子受体或跨膜激活剂和CAML相互作用。这些数据表明，CCR 5、CCR 6、CCR 7、CXCR 3、CXCR 4和CXCR 5可能在RA患者的B细胞迁移到滑膜中以及它们在滑膜中的局部增殖、细胞因子产生和ICOSL表达中起重要作用。
Accumulation of B cells in the rheumatoid arthritis (RA) synovium has been reported, and it has been thought that these cells might contribute to the pathogenesis of RA by antigen presentation, autoantibody production, and/or inflammatory cytokine production. Chemokines could enhance the accumulation of B cells in the synovium. The aims of this study were to determine chemokine receptor expression by B cells both in the peripheral blood of normal donors and subjects with RA, and at the inflammatory site in RA, and the effects of chemokines on B cell activation. Cell surface molecule expression was analyzed by flow cytometry. Cellular migration was assessed using chemotaxis chambers. Cellular proliferation was examined by 3H-thymidine incorporation. Tumor necrosis factor (TNF) production was assayed by enzyme-linked immunosorbent assay. Significant numbers of peripheral blood B cells of healthy donors and subjects with RA expressed CC chemokine receptor (CCR)5 and CXCR3, and most B cells expressed CCR6, CCR7, CXCR4 and CXCR5. CCR5 expression was more frequent on CD27+ than CD27- peripheral blood B cells of healthy donors and RA. Synovial B cells more frequently expressed CCR5, but less often expressed CCR6, CCR7 and CXCR5 compared to peripheral blood in RA. Further functional analyses were performed on peripheral blood B cells from healthy donors. Migration of peripheral blood B cells, especially CD27+ B cells, was enhanced by CC chemokine ligand (CCL)20, CCL19, CCL21 and CXCL12. All four chemokines alone induced B cell proliferation; with CCL21 being the most effective. CCL21 also enhanced the proliferation of anti-immunoglobulin (Ig)M-stimulated B cells and blockade of CCR7 inhibited this effect. CCL20, CCL21 and CXCL12 enhanced TNF production by anti-IgM mAb-stimulated B cells. Finally, stimulation with CXCL12, but not CCL20, CCL19 and CCL21, enhanced inducible costimulator-ligand (ICOSL) expression by peripheral blood B cells of healthy donors and RA, but did not increase B cell-activating factor receptor or transmembrane activator and CAML-interactor. The data suggest that CCR5, CCR6, CCR7, CXCR3, CXCR4 and CXCR5 may be important for the B cell migration into the synovium of RA patients, and also their local proliferation, cytokine production and ICOSL expression in the synovium.
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影响因子：
4.9
作者：
Mauri C;Ehrenstein MR
通讯作者：
Ehrenstein MR
影响因子：
--
作者：
LEE, SK;BRIDGES, SL;SCHROEDER, HW
通讯作者：
SCHROEDER, HW
影响因子：
--
作者：
Cohen, Stanley B.;Emery, Paul;Totoritis, Mark C.
通讯作者：
Totoritis, Mark C.
类风湿关节炎中滑膜细胞。树突状细胞。
影响因子：
4.9
作者：
Lutzky, Viviana;Hannawi, Suad;Thomas, Ranjeny
通讯作者：
Thomas, Ranjeny
影响因子：
11.4
作者：
Dürig, J;Schmücker, U;Dührsen, U
通讯作者：
Dührsen, U