Silverman G J, Carson D A
Department of Molecular and Experimental Medicine, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Eur J Immunol. 1990 Feb;20(2):351-6. doi: 10.1002/eji.1830200218.
Cold agglutinins that bind the developmentally regulated I red cell determinant occur naturally among human monoclonal IgM proteins. These autoantibodies are known to use light chains that derive mainly from the minor kappa III (kappa III) variable region subgroup. The kappa III subgroup is also highly expressed in monoclonal rheumatoid factors. However, while most monoclonal rheumatoid factors use structurally homologous heavy chains that derive from the VH1 family, information regarding the structure of the cold agglutinin heavy chains remains fragmentary. We demonstrate here that the kappa III cold agglutinin autoantibodies exclusively use heavy chains that derive from the VH4 family. Furthermore, these autoantibody heavy chains all express the same primary sequence-defined idiotype, corresponding to the second hypervariable region. These data indicate that cold agglutinins use a remarkably homogeneous subset of heavy chain variable regions. Moreover, unique patterns of preferential VH and VL pairing clearly distinguish the anti-I cold agglutinins from all other known monoreactive autoantibodies.
与发育调控的I红细胞决定簇结合的冷凝集素天然存在于人类单克隆IgM蛋白中。已知这些自身抗体使用的轻链主要来源于次要的κIII（kappa III）可变区亚组。κIII亚组在单克隆类风湿因子中也高度表达。然而，虽然大多数单克隆类风湿因子使用源自VH1家族的结构同源重链，但关于冷凝集素重链结构的信息仍然不完整。我们在此证明，κIII冷凝集素自身抗体仅使用源自VH4家族的重链。此外，这些自身抗体重链均表达相同的由一级序列定义的独特型，对应于第二个高变区。这些数据表明，冷凝集素使用重链可变区的一个非常同质的亚组。此外，VH和VL优先配对的独特模式清楚地将抗I冷凝集素与所有其他已知的单反应性自身抗体区分开来。
