Jin Juan, Gong Jianguang, Lin Bo, Li Yiwen, He Qiang
Department of Nephrology, Zhejiang Provincial People's Hospital, Zhejiang 310014, PR China; People's Hospital of Hangzhou Medical College, Zhejiang 310014, PR China.
Department of Nephrology, Zhejiang Provincial People's Hospital, Zhejiang 310014, PR China; People's Hospital of Hangzhou Medical College, Zhejiang 310014, PR China.
Mol Immunol. 2017 May;85:283-292. doi: 10.1016/j.molimm.2017.03.006. Epub 2017 Mar 27.
Fcγ receptors (FcγR) play a role in the acute rejection (AR) of organ transplants. FcγRIIB is an inhibitory FcγR expressed on B cells. Intravenous IgG (IVIG) and CD28 monoclonal antibody (mAb) have been shown to have immunomodulatory properties against AR.
To examine the association between FcγRIIB expression on B cell subpopulations and AR treatment efficacy.
Male F344 rats were used as kidney donors and Lewis rats as recipients to establish models of renal transplantation. Rats were divided into five groups: sham, AR-PBS, AR-IVIG, AR-PNGase F-IVIG, and AR-CD28. Serum creatinine (Scr), blood urea nitrogen (BUN), and urine protein content were determined. Inflammatory markers were measured by ELISA, FcγR by western blotting, and spleen B cell activation by flow cytometry.
Scr, BUN, urinary protein content, levels of CRP, IL-10, TNF-α, IL-6, IL-8, and IgG were all increased in the AR-PBS group compared with the sham group (all P<0.01); these increases were partly reversed in the AR-IVIG, AR-PNGase F IVIG, and AR-CD28 groups (all P<0.01), with IVIG showing the better efficacy than PNGase F IVIG. Furthermore, blood and spleen FcγRIA and FcγRIIIA were increased by AR, while FcγRIIB expressions in splenic activated B cells and regulatory B cells were decreased; these changes were partly alleviated by all three treatments, with IVIG having the better effect than PNGase F IVIG.
We observed an association between B cell FcγRIIB expression and treatment efficacy for AR after kidney transplantation in rats.
Fcγ受体(FcγR)在器官移植的急性排斥反应(AR)中起作用。FcγRIIB是一种在B细胞上表达的抑制性FcγR。静脉注射免疫球蛋白(IVIG)和CD28单克隆抗体(mAb)已被证明具有抗AR的免疫调节特性。
研究B细胞亚群上FcγRIIB表达与AR治疗效果之间的关联。
以雄性F344大鼠为肾脏供体,Lewis大鼠为受体建立肾移植模型。大鼠分为五组:假手术组、AR-PBS组、AR-IVIG组、AR-PNGase F-IVIG组和AR-CD28组。测定血清肌酐(Scr)、血尿素氮(BUN)和尿蛋白含量。通过酶联免疫吸附测定法(ELISA)测量炎症标志物,通过蛋白质免疫印迹法检测FcγR,通过流式细胞术检测脾脏B细胞活化情况。
与假手术组相比,AR-PBS组的Scr、BUN、尿蛋白含量、CRP、IL-10、TNF-α、IL-6、IL-8和IgG水平均升高(均P<0.01);在AR-IVIG组、AR-PNGase F-IVIG组和AR-CD28组中这些升高部分得到逆转(均P<0.01),IVIG显示出比PNGase F-IVIG更好的疗效。此外,AR使血液和脾脏中的FcγRIA和FcγRIIIA增加,而脾脏活化B细胞和调节性B细胞中的FcγRIIB表达降低;这三种治疗均部分缓解了这些变化,IVIG的效果优于PNGase F-IVIG。
我们观察到大鼠肾移植后B细胞FcγRIIB表达与AR治疗效果之间存在关联。