Barel M, Kahan A, Charriaut-Marlangue C, Kahan A, Frade R
Eur J Immunol. 1986 Nov;16(11):1357-61. doi: 10.1002/eji.1830161108.
gp140 is the Epstein-Barr virus receptor and the C3d receptor (EBVR/C3dR) of human B lymphocytes. Recently, we have shown that cross-linking of EBVR/C3dR on cell surface by polyclonal anti-gp140 induced B cell activation, in presence of T cell factors. Immunoregulatory abnormalities of EBV-induced B cell activation have been demonstrated in rheumatoid arthritis (RA) patients. These data prompted us to analyze the putative presence of anti-EBVR/C3dR autoantibodies in human sera. The IgG fractions from eleven RA and 10 normal sera were tested for their ability to: (a) bind to Raji cell surface; (b) inhibit the binding to cell surface of 3 anti-EBVR/C3dR monoclonal antibodies (mAb), which recognized different epitopes on gp140; (c) inhibit the binding of particle-bound C3d and (d) react with 1% Nonidet-P40-solubilized gp140 from Raji cell membranes, in immunoblotting assays. Three RA sera carry anti-EBVR/C3dR autoantibodies which react with gp140 expressed on Raji cell surface or its solubilized form. The purification of monomeric IgG fraction of selected RA sera ruled out involvement of immune complexes carrying C3 molecules, which could interfere in these assays. One of these 3 RA sera was able to inhibit the binding to cell surface of anti-EBVR/C3dR mAb and particle-bound C3d. However, the 2 other RA sera, found positive by immunoblotting, did not inhibit particle-bound C3d and presented differences in their inhibitory effect on anti-EBVR/C3dR mAb binding to Raji cell surface. These data allow us to demonstrate differences which exist in the properties of anti-EBVR/C3dR autoantibodies. These autoantibodies were not detected in all the normal and other RA sera. Anti-EBVR/C3dR autoantibodies could play a role "in vivo" in B lymphocyte activation of RA patients.
gp140是爱泼斯坦-巴尔病毒受体和人类B淋巴细胞的C3d受体（EBVR/C3dR）。最近，我们发现，在T细胞因子存在的情况下，多克隆抗gp140使细胞表面的EBVR/C3dR交联可诱导B细胞活化。在类风湿关节炎（RA）患者中已证实爱泼斯坦-巴尔病毒诱导的B细胞活化存在免疫调节异常。这些数据促使我们分析人血清中是否存在抗EBVR/C3dR自身抗体。检测了11份类风湿关节炎患者血清和10份正常血清的IgG组分，以评估它们：（a）与Raji细胞表面结合的能力；（b）抑制3种抗EBVR/C3dR单克隆抗体（mAb）与细胞表面结合的能力，这3种单克隆抗体识别gp140上不同的表位；（c）抑制颗粒结合的C3d的结合；以及（d）在免疫印迹分析中与Raji细胞膜上1% Nonidet-P40溶解的gp140发生反应的能力。3份类风湿关节炎患者血清携带抗EBVR/C3dR自身抗体，它们可与Raji细胞表面表达的gp140或其溶解形式发生反应。对选定的类风湿关节炎患者血清的单体IgG组分进行纯化，排除了携带C3分子的免疫复合物的干扰，因为这些免疫复合物可能会干扰这些检测。这3份类风湿关节炎患者血清中的1份能够抑制抗EBVR/C3dR单克隆抗体与细胞表面以及颗粒结合的C3d的结合。然而，另外2份经免疫印迹检测呈阳性的类风湿关节炎患者血清，并未抑制颗粒结合的C3d，并且在抑制抗EBVR/C3dR单克隆抗体与Raji细胞表面结合方面表现出差异。这些数据使我们能够证明抗EBVR/C3dR自身抗体在特性上存在差异。在所有正常血清和其他类风湿关节炎患者血清中均未检测到这些自身抗体。抗EBVR/C3dR自身抗体可能在类风湿关节炎患者的B淋巴细胞活化中“在体内”发挥作用。
