Yasmeen D, Ellerson J R, Dorrington K J, Painter R H
J Immunol. 1976 Feb;116(2):518-26.
The fragments related to the Cgamma2 and Cgamma3 homology regions of human IgG, described in the preceding paper by Ellerson, et al. were assayed for their ability to interact with complement, engage in cytophilic activity toward macrophages, and to play a role in controlling the catabolism of the whole IgG. The Cgamma2-fragment retained about 3% of the activity of intact IgG in a whole complement-fixing assay in which the test proteins were absorbed as mono-layers onto polystyrene latex beads. However, in a fluid-phase C1-binding assay this fragment showed the same activity as IgG and Fc fragment, when compared on a molar basis. Since the Cgamma2-fragment represented only one intact domain, full expression of complement-fixing activity appeared to be independent of quaternary interactions. Thus IgG possesses two C1-binding sites. The Cgamma3-fragment was inactive in both of the complement assays. The ability of IgG to interact with the Fc-receptor on guinea-pig macrophages was shown to be entirely a function of the Cgamma3 region. This was demonstrated both in a direct assay in which tanned red cells coated with Cgamma3-fragment formed rosettes with macrophages and in an indirect assay in which this fragment was able to inhibit rosette formation between IgG-coated red cells and macrophages. The rate of clearance of radiolabeled Cgamma2-, Cgamma3-, Fab, Fc fragments, and IgG from the circulation was measured in rabbits. The Cgamma2 fragment was cleared with a half-time similar to that shown by intact IgG and Fc (about 70 hr) whereas Cgamma3- and Fab fragments were cleared more rapidly (half-time, about 15 hr). The rate of cleaance was not related to the presence of sialic acid or exposed galactosyl residues at the termini of the carbohydrate prosthetic groups. These data clearly show that at least three of the biologic functions of IgG are mediated fully and independently by one or other of the Fc domains.
埃勒森等人在前一篇论文中描述的与人IgG的Cγ2和Cγ3同源区域相关的片段，被检测了它们与补体相互作用的能力、对巨噬细胞的嗜细胞活性以及在控制整个IgG分解代谢中所起的作用。在一项全补体固定试验中，将测试蛋白以单层形式吸附到聚苯乙烯乳胶珠上，Cγ2片段保留了完整IgG约3%的活性。然而，在液相C1结合试验中，以摩尔为基础比较时，该片段显示出与IgG和Fc片段相同的活性。由于Cγ2片段仅代表一个完整结构域，补体固定活性的充分表达似乎与四级相互作用无关。因此，IgG拥有两个C1结合位点。Cγ3片段在两种补体试验中均无活性。IgG与豚鼠巨噬细胞上Fc受体相互作用的能力被证明完全是Cγ3区域的功能。这在一项直接试验中得到了证明，即用Cγ3片段包被的鞣酸红细胞与巨噬细胞形成玫瑰花结，在一项间接试验中也得到了证明，即该片段能够抑制IgG包被的红细胞与巨噬细胞之间的玫瑰花结形成。在兔子中测量了放射性标记的Cγ2、Cγ3、Fab、Fc片段和IgG从循环中的清除率。Cγ2片段的清除半衰期与完整IgG和Fc相似（约70小时），而Cγ3和Fab片段清除得更快（半衰期约15小时）。清除率与碳水化合物辅基末端唾液酸或暴露的半乳糖基残基的存在无关。这些数据清楚地表明，IgG的至少三种生物学功能是由一个或另一个Fc结构域完全独立介导的。
