Comacchio R M, Bradley J, Hohmann A W
Department of Clinical Immunology, Flinders Medical Centre, Bedford Park, South Australia.
Immunol Cell Biol. 1996 Feb;74(1):72-80. doi: 10.1038/icb.1996.10.
Idiotypic networks have the capacity to exert significant influences on immune responses and an understanding of the ways to manipulate these networks may lead to new modalities in immunotherapy. In order to gain further insights into the nature of the immune responses stimulated by immunoglobulin idiotypes, rabbits were immunized with a mAb (Ab1) against a large globular protein, human albumin, or a mAb against a hapten, TNP. All rabbits developed anti-idiotypic antibodies (Ab2) and the rabbits immunized with anti-human albumin concomitantly developed antibodies to human albumin (Ab3). Ab2 prepared from these rabbits blocked binding of Ab1 to antigen and the anti-human albumin Ab2 reacted with all species of anti-human albumin including sheep, rabbit, rat and goat. The anti-TNP Ab2 reacted only with the mouse anti-TNP Ab1. This TNP Ab2 bound only to intact Ab1 whereas the human albumin Ab2 reacted with the Ab1 heavy chain. To compare the relative efficiencies of anti-idiotypic antibodies and antigen in inducing antibody, mice were immunized with rabbit Ab2 or antigen. All mice immunized with Ab2 developed anti-idiotypic Ab3, but only the human albumin Ab2 preparations elicited antigen specific Ab3; the amount of antibody produced was less than 1% of that found by immunization with antigen. The type of antibody induced in the Ab2-immunized mice was compared with that found in the antigen-immunized mice and in the Ab1-immunized rabbits. The mouse anti-albumin Ab3 was comparable to mouse Ab1 in terms of affinity and specificity for proteolytic fragments of human albumin. The Ab3 which arose in Ab1-immunized rabbits had a higher affinity and broader epitope specificity and was similar to antibodies raised against antigen. These results show considerable differences in the ability of similar anti-idiotypic antibodies to induce immune responses as well as considerable differences in the nature of a response seen within an intact network compared to an artificially induced network.
独特型网络有能力对免疫反应产生重大影响，了解操纵这些网络的方法可能会带来免疫治疗的新方式。为了进一步深入了解由免疫球蛋白独特型刺激的免疫反应的本质，用针对大球蛋白人白蛋白的单克隆抗体（Ab1）或针对半抗原TNP的单克隆抗体免疫兔子。所有兔子都产生了抗独特型抗体（Ab2），用抗人白蛋白免疫的兔子同时产生了抗人白蛋白抗体（Ab3）。从这些兔子制备的Ab2阻断了Ab1与抗原的结合，抗人白蛋白Ab2与包括绵羊、兔子、大鼠和山羊在内的所有抗人白蛋白物种发生反应。抗TNP Ab2仅与小鼠抗TNP Ab1反应。这种TNP Ab2仅与完整的Ab1结合，而人白蛋白Ab2与Ab1重链反应。为了比较抗独特型抗体和抗原诱导抗体的相对效率，用兔Ab2或抗原免疫小鼠。所有用Ab2免疫的小鼠都产生了抗独特型Ab3，但只有人白蛋白Ab2制剂引发了抗原特异性Ab3；产生的抗体量不到用抗原免疫所发现量的1%。将用Ab2免疫的小鼠中诱导的抗体类型与用抗原免疫的小鼠和用Ab1免疫的兔子中发现的抗体类型进行比较。小鼠抗白蛋白Ab3在对人白蛋白蛋白水解片段的亲和力和特异性方面与小鼠Ab1相当。在Ab1免疫的兔子中产生的Ab3具有更高的亲和力和更广泛的表位特异性，并且与针对抗原产生的抗体相似。这些结果表明相似的抗独特型抗体诱导免疫反应的能力存在显著差异，以及与人工诱导的网络相比，在完整网络中看到的反应本质也存在显著差异。
