Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Hefei 230032, Anhui Province, PR China.
Pharmacol Res. 2013 Feb;68(1):38-45. doi: 10.1016/j.phrs.2012.11.003. Epub 2012 Nov 22.
Anti-tumour necrosis factor-α (TNF-α) drugs are approved for the treatment of rheumatoid arthritis (RA). Many studies have investigated the effect of these drugs on the T cell response; however, some clues have indicated that it may also target B cells. This study was carried out to explore the potential effects and mechanisms of etanercept, a soluble TNF-α receptor, on the function of B cells and their development into memory B cells in type II collagen (CII)-induced arthritis (CIA). Beginning on day 24 after CII immunisation, the mice were evaluated every 2-3 days to determine two clinical parameters: their arthritis global assessment and swollen joint count (SJC). The serum concentrations of IgG1, IgG2a and anti-CII antibodies and the splenic pathology and proliferation of B cells were measured. The percentage of total memory B cells in the spleen was analysed with flow cytometry. BAFFR was detected by immunohistochemistry. In CIA mice, etanercept markedly suppressed the arthritis global assessment and the SJC, reduced the production of anti-CII, IgG1 and IgG2a antibodies, and prevented spleen histopathology to varying degrees; however, it had no obvious effect on splenic B cell proliferation. Etanercept also decreased the percentage of total CD27(+) memory B cells in the spleen. Treatment with etanercept was associated with a further increase in BAFFR expression, a significant reduction in CD27 expression, and a negative correlation between the levels of BAFFR and the percentage of memory B cells. Our findings showed that increased BAFFR expression has a regulatory effect on the activation of B cells and the generation of memory B cells, which may be one of the mechanisms of the therapeutic effects of etanercept.
抗肿瘤坏死因子-α（TNF-α）药物已被批准用于治疗类风湿关节炎（RA）。许多研究已经探讨了这些药物对 T 细胞反应的影响；然而，一些线索表明，它也可能针对 B 细胞。本研究旨在探讨可溶性 TNF-α受体依那西普对 II 型胶原（CII）诱导关节炎（CIA）中 B 细胞功能及其向记忆 B 细胞分化的潜在影响和机制。从 CII 免疫后第 24 天开始，每隔 2-3 天评估一次小鼠，以确定两个临床参数：关节炎总体评估和肿胀关节计数（SJC）。测量血清 IgG1、IgG2a 和抗 CII 抗体浓度以及脾组织病理学和 B 细胞增殖情况。用流式细胞术分析脾中总记忆 B 细胞的百分比。用免疫组化法检测 BAFFR。在 CIA 小鼠中，依那西普显著抑制关节炎总体评估和 SJC，降低抗 CII、IgG1 和 IgG2a 抗体的产生，并在不同程度上预防脾组织病理学改变；然而，它对脾 B 细胞增殖没有明显影响。依那西普还降低了脾中总 CD27（+）记忆 B 细胞的百分比。依那西普治疗与 BAFFR 表达进一步增加、CD27 表达显著降低以及 BAFFR 水平与记忆 B 细胞百分比之间呈负相关相关。我们的研究结果表明，BAFFR 表达增加对 B 细胞的激活和记忆 B 细胞的产生具有调节作用，这可能是依那西普治疗效果的机制之一。
