Schreiber A D, Frank M M
J Clin Invest. 1972 Mar;51(3):575-82. doi: 10.1172/JCI106846.
A model which permits evaluation in molecular terms of the role of antibody and of complement in the immune destruction of erythrocytes was established in the guinea pig. IgM and IgG immunoglobulins were isolated from rabbit anti-guinea pig erythrocyte antisera and were used to sensitize (51)Cr-labeled guinea pig erythrocytes. The average number of complement-fixing sites per erythrocyte formed by antibody was determined for each of the various preparations by the Cla fixation and transfer test. The rate of clearance and of organ localization was determined for cells sensitized with either IgM or IgG antibodies, and dose-response curves were established in normal guinea pigs and guinea pigs with a genetically controlled, complete absence of the fourth component of complement (C4). At least 60 complement-fixing sites per cell were required for accelerated clearance of IgM-sensitized erythrocytes. The bulk of cells with IgM sites were cleared by the liver within 5 min after injection and were then slowly returned to the circulation where they survived normally. There was no accelerated clearance whatsoever of IgM-sensitized erythrocytes in C4-deficient guinea pigs. As few as 1.4 IgG complement-fixing sites per cell resulted in decreased erythrocyte survival. There was no evidence of immediate tissue sequestration and release. Progressive trapping and destruction of erythrocytes by the spleen was responsible for most of the clearance of IgG-sensitized cells. Clearance of IgG-sensitized cells was markedly impaired in guinea pigs with C4 deficiency; however, there was some decrease over normal survival. The data indicate that IgG and IgM antibodies interact with complement in vivo by mechanisms which are qualitatively or quantitatively different and produce different biologic effects.
在豚鼠身上建立了一个模型，该模型能够从分子层面评估抗体和补体在红细胞免疫破坏过程中的作用。从兔抗豚鼠红细胞抗血清中分离出IgM和IgG免疫球蛋白，并用于使（51）Cr标记的豚鼠红细胞致敏。通过Cla固定和转移试验，对各种制剂中每个红细胞由抗体形成的补体结合位点的平均数进行了测定。测定了用IgM或IgG抗体致敏的细胞的清除率和器官定位率，并在正常豚鼠和基因控制的完全缺乏补体第四成分（C4）的豚鼠中建立了剂量反应曲线。IgM致敏红细胞的加速清除需要每个细胞至少60个补体结合位点。带有IgM位点的大部分细胞在注射后5分钟内被肝脏清除，然后缓慢返回循环系统并正常存活。在缺乏C4的豚鼠中，IgM致敏红细胞没有任何加速清除的情况。每个细胞低至1.4个IgG补体结合位点就会导致红细胞存活率降低。没有立即组织隔离和释放的证据。脾脏对IgG致敏细胞的逐步捕获和破坏是其清除的主要原因。在缺乏C4的豚鼠中，IgG致敏细胞的清除明显受损；然而，与正常存活率相比仍有一些下降。数据表明，IgG和IgM抗体在体内与补体相互作用的机制在质或量上有所不同，并产生不同的生物学效应。
