GENETICS AND REGULATION OF THE IG VH REGION

这项研究代表了对遗传和遗传基础研究的继续 注重变量的免疫球蛋白生产调控 重链的区域(VH)。在这些研究中使用兔子是因为 其明确的基因决定的VH同种异型和独特的 针对这些同种异型的抗体特征。两国关系 VH同种异型和免疫球蛋白独特型之间的关系将被研究 从两个角度来看。在一个项目中，VH与 将通过分析交叉反应的发生来探测亚群 表达VH亚群的Ig群体之间和群体内的独特型。 将抗独特型抗血清提纯为抗一种简单和一种 复杂的抗原。在这些患者中出现交叉反应独特型 实验将支持涉及网络监管的理论 相互作用，并可能指示共同的遗传因素 远亲VH亚群。或者，独特型的存在 其被限制在给定子组中。一秒钟内 系列实验，将VH同种异型作为抗原诱导 抗同种异型抗体。这种抗体已经被证明表达一种 所有兔的交叉反应独特型比例都很高 测试过。这些观察结果导致人们猜测，抗同种异体 兔子的剧目高度保守，暗示着它 在调节同种异型表达方面起着重要作用。一直以来 进一步提出了同种异型、抗同种异型、抗独特型网络 是作为连续的负正立体图像的结果产生的 (内部图像)。我们建议通过比较以下各项来检验这些假设 抗体的免疫生物学和免疫化学特性 兔饲养的制剂与其他非兔饲养的制剂相比 物种。这些比较将使用常规的 血清学方法(放射免疫分析、亲和层析、等电 聚焦)以及通过使用同种异型和独特型抑制， 单抗和免疫电子显微镜。规管 免疫球蛋白的产生对某些疾病具有重要的意义 免疫缺陷疾病的类型以及骨髓瘤和白血病。

This study represents a continuation of basic research on the genetics and regulation of immunoglobulin production with emphasis on the variable region (VH) of the heavy chain. The rabbit is used in these studies due to its well defined genetically-determined VH allotypes and the unique characteristics of antibody against these allotypes. The relationship between the VH allotypes and immunoglobulin idiotypes will be investigated from two perspectives. In one project the relationship between VH subgroups will be probed by assaying for the occurrence of crossreactive idiotypes between and within Ig populations expressing the VH subgroups. Anti-idiotype antisera will be raised against antibody to a simple and a complex antigen. The occurrence of crossreactive idiotypes in these experiments would support theories involving network regulatory interactions and might be indicative of shared genetic elements between distantly related VH subgroups. Alternatively, the presence of idiotypes which are restricted to a given subgroup may be revealed. In a second series of experiments, VH allotypes will be used as an antigen to induce anti-allotype antibody. This antibody has already been shown to express a remarkably high proportion of crossreactive idiotype in all rabbits tested. These observations have lead to speculation that the anti-allotype repertoire of the rabbit is highly conserved with the implication that it serves an important role in regulating allotype expression. It has been further suggested that the allotype, anti-allotype, anti-idiotype network is generated as a result of sequential negative and positive steric images (internal images). We propose to test these assumptions by comparing the immunobiological and immunochemical characteristics of antibody preparations raised in the rabbit to those raised in other non-rabbit species. The comparisons will be carried out using conventional serological methods (radioimmunoassay, affinity chromatography, isoelectric focusing) as well as by the use of allotype and idiotype suppression, monoclonal antibodies and immunoelectron microscopy. Regulation of immunoglobulin-production has important implications with regard to certain types of immunodeficiency diseases as well as myelomas and leukemias.