Henneken Maren, Dörner Thomas, Burmester Gerd-Rüdiger, Berek Claudia
Deutsches Rheuma ForschungsZentrum, Berlin, Germany.
Arthritis Res Ther. 2005;7(5):R1001-13. doi: 10.1186/ar1776. Epub 2005 Jun 22.
Chemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.
趋化因子及其受体在淋巴细胞的募集和定位过程中起着至关重要的作用。为了探究类风湿性关节炎(RA)患者炎症滑膜组织中B细胞迁移的问题,我们分析了外周血中的初始B细胞、记忆B细胞和浆细胞,检测其趋化因子受体CXCR3、CXCR4、CXCR5、CCR5、CCR6、CCR7和CCR9的细胞表面表达情况。作为对照,我们还分析了自身免疫性疾病系统性红斑狼疮(SLE)患者和退行性疾病骨关节炎(OA)患者外周血中的B细胞。通过流式细胞术测定趋化因子受体的表达水平,并在不同患者组和健康个体之间进行比较。趋化因子受体表达分析表明,大多数外周血B细胞CXCR3、CXCR4、CXCR5、CCR6和CCR7呈阳性。仅有一小部分B细胞CCR5呈阳性,几乎未发现CCR9的表达。与健康个体相比,RA患者中有相当一部分B细胞CXCR5和CCR6表达降低,CXCR3水平升高。CXCR5的下调与CXCR3的上调相关。SLE患者CXCR5表达有显著变化。分别通过趋化因子CXCL10和CXCL12的迁移试验证明了趋化因子受体CXCR3和CXCR4的功能。我们的结果表明,慢性炎症会导致外周血B细胞趋化因子受体表达的调节。然而,RA患者和SLE患者之间的差异表明受体表达存在疾病特异性调节。这些差异可能会影响B细胞的迁移行为。