Brown J C, Rodkey L S
J Exp Med. 1979 Jul 1;150(1):67-85. doi: 10.1084/jem.150.1.67.
The antibody response of a single outbred rabbit was studied throughout three rounds of injections with Micrococcus lysodeikticus vaccine over a 31-mo period. The first-round response was characterized by a vigorous anti- micrococcus response and a strong anti-IgG rheumatoid factor response. The second-round response consisted of a triad of interacting molecules: anti- micrococcal antibodies, autoanti-idiotypic antibodies specific for distinct clonotypes of the first-round anti-micrococcal antibodies, and Fc-specific anti-IgG rheumatoid factor. The interacting triple complex was detected because of the formation of an immune complex that became insoluble upon dilution of the serum. Complex formation was inhibited in the presence of saccharide compounds known to be major immunodominant determinants of the micrococcal cell-wall carbohydrate polymer. The same saccharides did not affect the reaction of rheumatoid factor with IgG. Direct-binding radioimmunoassays ruled out mediation of the dilution-precipitation reaction by soluble micrococcal antigens. Specific absorption of rheumatoid factor inhibited the dilution-precipitation reaction. Auto-anti-idiotypic antibodies were specifically purified from second-round sera, directly confirming the presence of these antibodies. Suppressive effects of auto-anti-idiotypic antibodies on distinct antibody clonotypes were shown by gel isoelectric focusing of first-, second-, and third-round sera. Clonotypes expressed in the first round of immunizations were reduced in quantity or absent when auto-anti-idiotypic antibodies were detectable. Greatly enhanced levels or initial synthesis of new clonotypes of anti-micrococcal antibodies were detected during the period of auto-anti-idiotype synthesis. The third-round sera, devoid of detectable auto-anti-idiotype, contained clonotypes characteristic of both first- and second-round antisera. Thus, auto-anti- idiotypic-mediated suppression appeared to be reversible. The data are interpreted as lending strong support for concepts of autoregulation of immune processes in normal outbred animals via an idiotypic network.
在31个月的时间里，对一只远交系兔子在三轮注射溶壁微球菌疫苗后的抗体反应进行了研究。第一轮反应的特征是强烈的抗微球菌反应和强烈的抗IgG类风湿因子反应。第二轮反应由一组相互作用的分子组成：抗微球菌抗体、针对第一轮抗微球菌抗体不同克隆型的自身抗独特型抗体，以及Fc特异性抗IgG类风湿因子。由于形成了一种免疫复合物，该复合物在血清稀释后变得不溶，因此检测到了相互作用的三联复合物。在已知是微球菌细胞壁碳水化合物聚合物主要免疫显性决定簇的糖类化合物存在的情况下，复合物的形成受到抑制。相同的糖类并不影响类风湿因子与IgG的反应。直接结合放射免疫测定排除了可溶性微球菌抗原介导稀释沉淀反应的可能性。类风湿因子的特异性吸收抑制了稀释沉淀反应。从第二轮血清中特异性纯化了自身抗独特型抗体，直接证实了这些抗体的存在。通过对第一轮、第二轮和第三轮血清进行凝胶等电聚焦，显示了自身抗独特型抗体对不同抗体克隆型的抑制作用。当可检测到自身抗独特型抗体时，第一轮免疫中表达的克隆型数量减少或缺失。在自身抗独特型合成期间，检测到抗微球菌抗体新克隆型的水平大大提高或开始合成。第三轮血清中没有可检测到的自身抗独特型，含有第一轮和第二轮抗血清特有的克隆型。因此，自身抗独特型介导的抑制似乎是可逆的。这些数据被解释为有力支持了正常远交系动物通过独特型网络对免疫过程进行自身调节的概念。
