Synergistic deposition of c4d by complement-activating and non-activating antibodies in cardiac transplants
Synergistic deposition of c4d by complement-activating and non-activating antibodies in cardiac transplants
复制标题
DOI：
10.1111/j.1600-6143.2007.01971.x
复制
发表时间：
2007-11-01
影响因子：
8.8
通讯作者：
Wasowska, B. A.
中科院分区：
文献类型：
--
作者：
Murata, K.;Fox-Talbot, K.;Wasowska, B. A.
非补体激活同种抗体在体液移植排斥反应中的作用尚不清楚。我们假设非补体激活同种抗体协同激活补体与补体激活抗体。将B10.A心脏移植到用针对MHC I类抗原的单克隆抗体重建的免疫球蛋白敲除（Ig-KO）小鼠中。在未重建的Ig-KO受体的同种异体移植物中，未检测到C4d。同样，用IgG 1或低剂量IgG 2b同种抗体重建也不会诱导C4 d沉积。然而，给予低剂量IgG 2b和IgG 1的小鼠在血管内皮上有大量的C4d线性沉积。C4d沉积与移植物存活率降低相关。为了在体外复制这种协同作用，将来自B10.A小鼠的单核细胞与针对MHC I类抗原的抗体一起孵育，然后在正常小鼠血清中孵育。流式细胞术显示IgG 2a和IgG 2b均与IgG 1协同作用，使C4 d存款。这种协同作用显着降低小鼠血清中缺乏甘露糖结合凝集素（MBL）和血清中缺乏C1 q。用C1 q敲除（C1 q-KO）血清重建MBL-A/C敲除（MBL-KO）血清重新建立了协同活性。这表明非补体激活同种抗体和MBL在体液排斥反应中的新作用。
The role of non-complement-activating alloantibodies in humoral graft rejection is unclear. We hypothesized that the non-complement-activating alloantibodies synergistically activate complement in combination with complement-activating antibodies. B10.A hearts were transplanted into immunoglobulin knock out (Ig-KO) mice reconstituted with monoclonal antibodies to MHC class I antigens. In allografts of unreconstituted Ig-KO recipients, no C4d was detected. Similarly, reconstitution with IgG1 or low dose IgG2b alloantibodies did not induce C4d deposition. However, mice administered with a low dose of IgG2b combined with IgG1 had heavy linear deposits of C4d on vascular endothelium. C4d deposits correlated with decreased graft survival. To replicate this synergy in vitro, mononuclear cells from B10.A mice were incubated with antibodies to MHC class I antigens followed by incubation in normal mouse serum. Flow cytometry revealed that both IgG2a and IgG2b synergized with IgG1 to deposit C4d. This synergy was significantly decreased in mouse serum deficient in mannose binding lectin (MBL) and in serum deficient in C1q. Reconstitution of MBL-A/C knock out (MBL-KO) serum with C1q-knock out (C1q-KO) serum reestablished the synergistic activity. This suggests a novel role for non-complement-activating alloantibodies and MBL in humoral rejection.