Dixon F J, Jacot-Guillarmod H, McConahey P J
J Exp Med. 1967 Jun 1;125(6):1119-35. doi: 10.1084/jem.125.6.1119.
Suppression of the primary response of rabbits to intravenously administered KLH can be achieved with very small amounts of hyperimmune anti-KLH administered a day later since the rabbit apparently rapidly eliminates most of the KLH by nonimmunologic means. The amount of passive anti-KLH needed to achieve immunosuppression was directly proportional to the dose of injected antigen. Antibody passively administered as much as 6-8 days after antigen still can be strongly immunosuppressive, which suggests that the antibody must be reacting with immunogen in or on responding cells or perhaps in the process of transfer between cells. There was no evidence that the presence of passively administered hyperimmune anti-KLH prior to the injection of antigen had any immunosuppressive action beyond the direct neutralization of the injected antigen. When KLH was injected in Freund adjuvant, anti-KLH incorporated with the KLH in the adjuvant was much more efficient in causing immunosuppression than anti-KLH given intravenously. The primary responses to 2 mg KLH given intravenously and 2 microg given in adjuvant reached approximately equal peaks and were suppressible by comparable amounts of intravenously administered anti-KLH. Two observations suggest that passive antibody neutralizes the immunogenic stimulus at the level of individual antigenic determinants and not merely by aggregating or precipitating entire antigenic molecules. First, anti-abalone hemocyanin (AH) which cross-reacts approximately 50% with KLH was only partially immunosuppressive even in extremely large amounts, i.e., amounts which could react with and precipitate much more KLH than could the smaller but more suppressive doses of anti-KLH. Second, when KLH and anti-KLH were given together in adjuvant, effective immunosuppression was achieved only with amounts of anti-KLH sufficient to saturate or cover virtually all available antigenic determinants. The immunosuppressive quality of passive antibody increases with time after immunization and with repeated immunization of the donor. In view of their relatively weak immunosuppressive properties, antibodies formed in the first weeks of a primary response may not contribute significantly to the turning off of the antibody response. In any event, results obtained by passive transfer of hyperimmune antibody to animals early in a primary response cannot be applied to the natural events in a primary response.
由于兔子显然能通过非免疫方式迅速清除大部分钥孔戚血蓝蛋白（KLH），所以在静脉注射KLH一天后给予极少量的超免疫抗KLH，就能抑制兔子的初次反应。实现免疫抑制所需的被动抗KLH量与注射抗原的剂量直接成正比。在抗原注射后多达6 - 8天被动给予的抗体仍具有很强的免疫抑制作用，这表明抗体必定是在反应细胞内或细胞表面与免疫原发生反应，或者可能是在细胞间传递过程中发生反应。没有证据表明在注射抗原之前给予被动超免疫抗KLH除了直接中和注射的抗原外还有任何免疫抑制作用。当KLH与弗氏佐剂一起注射时，与佐剂中KLH结合的抗KLH在引起免疫抑制方面比静脉注射的抗KLH效率高得多。对静脉注射2mg KLH和在佐剂中注射2μg KLH的初次反应达到大致相同的峰值，并且可被相当量的静脉注射抗KLH抑制。两项观察结果表明，被动抗体是在单个抗原决定簇水平上中和免疫原性刺激，而不仅仅是通过聚集或沉淀整个抗原分子。首先，与KLH有大约50%交叉反应的抗鲍鱼血蓝蛋白（AH）即使大量存在也只是部分具有免疫抑制作用，即与较小但更具抑制作用的抗KLH剂量相比，其能与更多KLH反应并沉淀的量，却只能产生部分免疫抑制。其次，当KLH和抗KLH在佐剂中一起给予时，只有抗KLH量足以饱和或覆盖几乎所有可用抗原决定簇时才能实现有效的免疫抑制。被动抗体的免疫抑制特性随着免疫后时间的推移以及供体的重复免疫而增强。鉴于其相对较弱的免疫抑制特性，在初次反应的最初几周形成的抗体可能对关闭抗体反应没有显著贡献。无论如何，在初次反应早期将超免疫抗体被动转移到动物身上所获得的结果不能应用于初次反应中的自然情况。
