Schreiber A D, Frank M M
J Clin Invest. 1972 Mar;51(3):583-9. doi: 10.1172/JCI106847.
A model for the immune clearance and destruction of homologous erythrocytes has been further explored. In this model, every IgM anti-erythrocyte antibody molecule in an antibody preparation was shown to fix Cl. About 2000 IgG antibody molecules were required to form a Cl-fixing site on the guinea pig erythrocyte surface. 60 IgM complement-fixing sites per erythrocyte were required for the immune clearance of IgM-sensitized erythrocytes. This number of sites could be detected by a direct agglutination test. 1.4 complement-fixing sites were required for immune clearance of IgG-sensitized cells, a number of molecules which could not be detected by direct agglutination. This number could, however, be detected with the use of a Coombs antiglobulin reagent. Depletion of the late components of complement (C3-9) with cobra venom was associated with the loss of ability to clear IgM-sensitized cells and a marked deficit in the ability to clear IgG-coated cells. Thus, late (C3-9) components of complement as well as an early component (C4) were required for normal clearance of sensitized erythrocytes. There was no evidence that activation of the alternate pathway of complement action could lead to accelerated erythrocyte clearance. In vitro incubation of IgG and IgM-sensitized erythrocytes in fresh serum led to deposition of C3 and C4 on the erythrocyte surface. IgM-sensitized cells treated in this way had a normal survival. IgM-sensitized cells also were shown to remain Coombs positive after their release from the liver. The evidence suggests that the interaction of an IgM site with fresh serum in vitro and in vivo leads to formation of a site which allows for sequestration of cells in the liver. With continued exposure to serum components, this site is destroyed or inactivated. This serum-dependent inactivation is complement-dependent as shown by the use of EDTA-treated and C4-deficient serum. IgG complement-fixing sites are only partially inactivated by incubation in fresh serum, further emphasizing the differences in the biologic activity of IgM and IgG antibodies.
一种关于同源红细胞免疫清除与破坏的模型已得到进一步探究。在该模型中，抗体制剂中的每一个IgM抗红细胞抗体分子都显示能固定补体C1。在豚鼠红细胞表面形成一个补体C1固定位点大约需要2000个IgG抗体分子。IgM致敏红细胞的免疫清除需要每个红细胞有60个IgM补体固定位点。这个位点数量可通过直接凝集试验检测到。IgG致敏细胞的免疫清除需要1.4个补体固定位点，这一分子数量无法通过直接凝集试验检测到。然而，使用库姆斯抗球蛋白试剂可以检测到这个数量。用眼镜蛇毒消耗补体的后期成分（C3 - 9）与清除IgM致敏细胞能力的丧失以及清除IgG包被细胞能力的显著缺陷有关。因此，补体的后期（C3 - 9）成分以及早期成分（C4）是致敏红细胞正常清除所必需的。没有证据表明补体作用的替代途径激活能导致红细胞清除加速。IgG和IgM致敏红细胞在新鲜血清中进行体外孵育会导致C3和C4沉积在红细胞表面。以这种方式处理的IgM致敏细胞具有正常的存活时间。IgM致敏细胞从肝脏释放后也显示仍为库姆斯阳性。证据表明，IgM位点在体外和体内与新鲜血清的相互作用会导致形成一个位点，该位点允许细胞在肝脏中被隔离。随着持续暴露于血清成分，这个位点会被破坏或失活。如使用经乙二胺四乙酸（EDTA）处理的血清和C4缺陷血清所示，这种血清依赖性失活是补体依赖性的。IgG补体固定位点在新鲜血清中孵育时仅部分失活，这进一步强调了IgM和IgG抗体生物活性的差异。
