Pascual V, Victor K, Spellerberg M, Hamblin T J, Stevenson F K, Capra J D
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-9048.
J Immunol. 1992 Oct 1;149(7):2337-44.
We previously reported that human autoantibodies with cold agglutinin activity contained a single human VH gene segment (VH4-21) which was also responsible for the cross-idiotypic specificity characteristic of the cold agglutinin response. To confirm and extend this observation we have analyzed at the nucleotide level the H and L chains of six new cold agglutinin molecules derived from different patients. We found that regardless of whether the antibody recognizes the i or the I red cell Ag, restriction at the VH gene segment level is absolute. We also found that even in the absence of somatic mutation the VH4-21 gene segment can encode both anti-i and anti-I specificities. Finally, although the VH4-21 gene segment is essential for cold agglutinin activity, the other genetic elements that contribute to the V region of the antibody molecules can be extremely diverse. The structural information provided in this report sharply restricts the requirement for encoding pathogenic cold agglutinin activity to one of the components of the H chain V region, specifically the VH gene segment. The implications of this apparently absolute requirement for a single VH gene segment, unprecedented in the human autoimmune response, are discussed.
我们先前报道过，具有冷凝集素活性的人类自身抗体包含一个单一的人类VH基因片段（VH4-21），该片段也负责冷凝集素反应的交叉独特型特异性。为了证实并扩展这一观察结果，我们在核苷酸水平分析了来自不同患者的六个新冷凝集素分子的重链和轻链。我们发现，无论抗体识别的是i还是I红细胞抗原，VH基因片段水平的限制都是绝对的。我们还发现，即使在没有体细胞突变的情况下，VH4-21基因片段也可以编码抗i和抗I特异性。最后，虽然VH4-21基因片段对于冷凝集素活性至关重要，但构成抗体分子V区的其他遗传元件可能极其多样。本报告中提供的结构信息将致病性冷凝集素活性的编码要求严格限制在重链V区的一个组成部分，即VH基因片段。本文讨论了这种对单一VH基因片段的明显绝对要求在人类自身免疫反应中前所未有的意义。
