Natori T
Hokkaido Igaku Zasshi. 1983 Jul;58(4):420-8.
A population of Fab fragments was identified in the papain-solubilized fraction of membranes of a rat chemically-induced sarcoma, KMT 17. The Fab fragments were partially purified by gel filtration and column electrophoresis. A rabbit antiserum against the partially purified Fab fragments was raised and shows to be specific for Fab fragments by immunoelectrophoresis. Furthermore, four lines of evidence supported that the KMT 17 Fab-fragments carry a cross-reactive idiotype; 1) the antiserum could bind only with a restricted population of normal Fab fragments having pI of 6.3, 2) an unrelated antibody (WKA anti-SRBC) showed a weak cross-reactivity (less than 6%), 3) syngeneic antisera against the KMT 17 could bind with the 125I-KMT 17 Fab preparation that was purified by an immunoabsorbent column with the rabbit anti-KMT 17 Fab antiserum (anti-idiotype antibody), 4) the rabbit anti-KMT 17 Fab antiserum could bind with neither heavy nor light chains of WKA IgG. The natural antibody carrying the idiotype was found in normal serum and in various organs as well, especially in the lung of the conventional rats. In addition, the fractions containing Fab fragments (FrII) were shown to have enhancing activity of the tumor growth when they were injected into syngeneic animals. Whereas Fab-free fractions that were separated from the Fab fragments by column electrophoresis showed no enhancing activity. These results suggested strongly that a population of Fab fragments carrying a cross-reactive idiotype was responsible for the enhancement of tumor growth. Mechanisms for the biological function of natural anti-tumor antibodies carrying a cross-reactive idiotype were discussed.
在大鼠化学诱导肉瘤KMT 17的膜木瓜蛋白酶可溶部分中鉴定出一群Fab片段。通过凝胶过滤和柱电泳对Fab片段进行了部分纯化。制备了针对部分纯化的Fab片段的兔抗血清,并通过免疫电泳证明其对Fab片段具有特异性。此外,有四条证据支持KMT 17 Fab片段携带交叉反应独特型:1)抗血清仅能与pI为6.3的有限群体的正常Fab片段结合;2)一种无关抗体(WKA抗SRBC)显示出较弱的交叉反应性(小于6%);3)针对KMT 17的同基因抗血清可与用兔抗KMT 17 Fab抗血清(抗独特型抗体)通过免疫吸附柱纯化的125I-KMT 17 Fab制剂结合;4)兔抗KMT 17 Fab抗血清既不能与WKA IgG的重链也不能与轻链结合。携带该独特型的天然抗体在正常血清以及各种器官中均有发现,尤其是在传统大鼠的肺中。此外,当将含有Fab片段的组分(FrII)注射到同基因动物体内时,显示出具有促进肿瘤生长的活性。而通过柱电泳从Fab片段中分离出的无Fab组分则没有促进活性。这些结果有力地表明,携带交叉反应独特型的一群Fab片段是肿瘤生长增强的原因。讨论了携带交叉反应独特型的天然抗肿瘤抗体的生物学功能机制。