The First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Japan.
Mitsubishi Tanabe Pharma Corporation, UK.
Clin Immunol. 2019 Mar;200:1-9. doi: 10.1016/j.clim.2018.12.017. Epub 2018 Dec 19.
Memory B cells are increased in systemic lupus erythematosus (SLE) cases, but the qualitative abnormalities and induction mechanism of these cells are unclear. Here, we subclassified B cells by their chemokine receptor expression and investigated their induction mechanism. The peripheral blood of patients with SLE showed higher levels of CXCR5 and CXCR3 B cells. CXCR5CXCR3 B cell levels were elevated in patients with active SLE, which decreased with improving disease conditions. Interferon (IFN)-γ stimulation increased CXCR3 expression, whereas IFN-β stimulation reduced CXCR5 expression in B cells. Furthermore, CXCR5CXCR3 B cells were induced by a combination of IFN-β and IFN-γ stimulation. Renal tissue examination of patients with active lupus nephritis confirmed the presence of CD19CXCR3 B cells. Collectively, the results revealed qualitative abnormalities accompanying reduced CXCR5 expression via type I IFN and enhanced CXCR3 expression via type II IFN in SLE, suggesting their involvement in B cell infiltration into tissues and inflammatory pathogenesis.
记忆 B 细胞在系统性红斑狼疮(SLE)患者中增加,但这些细胞的定性异常和诱导机制尚不清楚。在这里,我们根据趋化因子受体表达对 B 细胞进行了分类,并研究了它们的诱导机制。SLE 患者的外周血显示出更高水平的 CXCR5 和 CXCR3 B 细胞。活跃性 SLE 患者的 CXCR5CXCR3 B 细胞水平升高,随着病情的改善而降低。IFN-γ 刺激增加了 CXCR3 的表达,而 IFN-β 刺激减少了 B 细胞中 CXCR5 的表达。此外,IFN-β 和 IFN-γ 刺激的组合诱导了 CXCR5CXCR3 B 细胞。对活动性狼疮肾炎患者的肾组织检查证实了存在 CD19CXCR3 B 细胞。综上所述,结果表明,SLE 中通过 I 型 IFN 降低 CXCR5 表达和通过 II 型 IFN 增强 CXCR3 表达伴随着定性异常,提示它们参与了 B 细胞浸润到组织和炎症发病机制中。