Cheng Si, He Chao, Zhou Hong, Kong Xiangmin, Xie Hongxiang, Xia Longfei, Yan Jinchuan
Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212013, PR China; Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
Department of Clinical Laboratory and Hematology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
Mol Immunol. 2016 Mar;71:78-86. doi: 10.1016/j.molimm.2016.01.012. Epub 2016 Feb 9.
Our previous study demonstrated that Toll-like receptor 4 (TLR4) plays a vital role in the maturation of bone marrow-derived dendritic cells (BMDCs) from the mice immunized with human β2-glycoprotein I (β2GPI). However, the roles of TLR4 in the activation of B cells and production of anti-β2GPI antibodies in vivo have been rarely studied. This study aimed to investigate the activation of B cells from TLR4-defective (C3H/HeJ) and TLR4-intact (C3H/HeN) mice pre-immunized with human β2GPI. After β2GPI injection, the level of anti-β2GPI antibody in the serum of TLR4-defective and TLR4-intact mice was gradually increased and the number and size of germinal centers in the spleen were also significantly increased. Compared with C3H/HeJ mice, we observed significantly higher anti-β2GPI antibody titer and more germinal centers in C3H/HeN mice. Moreover, the β2GPI-induced expression of CD40L, CD40, CD80, CD86 and MHC II in C3H/HeN mice was significantly higher than that in C3H/HeJ mice. Furthermore, the β2GPI-induced expression of B cell activating factor (BAFF) in the spleen and IL-6 and IL-10 in B cells from C3H/HeN mice was also significantly increased compared to C3H/HeJ mice. Taken together, our results suggest that TLR4 is required for the activation of B cells and the production of autoantibody in mice treated with β2GPI, but the immunological mechanisms of antiphospholipid syndrome (APS) need further investigation.
我们先前的研究表明，在用人β2糖蛋白I（β2GPI）免疫的小鼠中，Toll样受体4（TLR4）在骨髓来源的树突状细胞（BMDCs）成熟过程中发挥着至关重要的作用。然而，TLR4在体内B细胞激活和抗β2GPI抗体产生中的作用鲜有研究。本研究旨在探讨预先用人β2GPI免疫的TLR4缺陷（C3H/HeJ）小鼠和TLR4完整（C3H/HeN）小鼠中B细胞的激活情况。注射β2GPI后，TLR4缺陷和TLR4完整小鼠血清中抗β2GPI抗体水平逐渐升高，脾脏中生发中心的数量和大小也显著增加。与C3H/HeJ小鼠相比，我们观察到C3H/HeN小鼠中抗β2GPI抗体滴度显著更高，生发中心更多。此外，β2GPI诱导的C3H/HeN小鼠中CD40L、CD40、CD80、CD86和MHC II的表达显著高于C3H/HeJ小鼠。此外，与C3H/HeJ小鼠相比，β2GPI诱导的C3H/HeN小鼠脾脏中B细胞活化因子（BAFF）以及B细胞中IL-6和IL-10的表达也显著增加。综上所述，我们的结果表明，在用β2GPI处理的小鼠中，TLR4是B细胞激活和自身抗体产生所必需的，但抗磷脂综合征（APS）的免疫机制仍需进一步研究。
