PATHOGENESIS OF EXPERIMENTAL GLOMERULONEPHRITIS

本研究项目的目的是分析抗体的作用机制。 诱导大鼠肾小球肾炎(GN)时的靶抗原 决定簇是单个明确定义的结构，通过使用单克隆化 (杂交瘤)抗体作为特异性探针。我们将生产老鼠 抗大鼠肾小球基底膜蛋白杂交瘤及 培养的肾小球细胞，并初步定义了 产生的单抗(免疫球蛋白的类别和亚类， 修复补体的能力和良好的特异性)。不同的单抗 抗体制剂将被被动地注射给大鼠以产生 肾小球功能和形态异常。致肾病和 非致肾炎抗体将与 与肾脏的结合，周转率，结合的局部化和能力 固定补语，以期定义异源的属性 对诱发被动性肾炎至关重要的抗体。目标是 致肾性和非致肾性抗体的抗原将是 从溶解的GBM制剂中纯化，使用抗体作为 特异性免疫吸收剂。这些抗原将被表征，他们的 肾内定位由抗体结合决定。最后， 将尝试通过以下方式诱导一种活跃的、自身免疫形式的GN 用纯化的自体抗原免疫动物，并免疫 这种ANTO免疫性GN的发病机制将是 通过体外实验和过继转移实验进行分析。

The goal of this research project is to analyze the mechanisms of antibody induced glomerulonephritis (GN) in rats when the target antigenic determinant is a single well-defined structure, by using monoclonal (hybridoma) antibodies as specific probes. We will produce mouse hybridomas against rat glomerular basement membrane (GBM) proteins and cultured glomerular cells, and initially define the properties of the resultant monoclonal antibodies (class and subclass of immunoglobulin, ability to fix complement and fine specificity). Different monoclonal antibody preparations will be passively administered to rats to produce functional and morphologic glomerular abnormalities. Nephritogenic and non-nephritogenic antibodies will be compared with respect to quantity of binding to kidneys, turnover rates, localization of binding and ability to fix complement with a view to defining the properties of heterologous antibodies that are critical for the induction of passive GN. The target antigens for nephritogenic and non-nephritogenic antibodies will be purified from solubilized GBM preparations, using the antibodies as specific immunoabsorbents. These antigens will be characterized, and their localization in the kidneys determined by antibody binding. Finally, attempts will be made to induce an active, auto-immune form of GN by immunizing animals with purified autologous antigens, and the immune mechanisms involved in the pathogenesis of this anto-immune GN will be analyzed by in vitro tests and adoptive transfer experiments.