BIOLOGY AND BIOCHEMISTRY OF THE C3B RECEPTOR

与自身免疫性疾病相关的补体系统的两种功能是 炎症反应的诱导和 免疫反应 对两种补体受体的研究提出， 解决这两个功能。 一组血浆和膜蛋白共享 结构基序抑制经典的C3/C5转化酶步骤， 替代途径。 这个家族的一员，补体受体 1型（CR 1; CD 35）通常作为受体，但特别适合于 用于补体抑制 CRI将双链体结合至C3 b的二聚体， C4 b，促进它们被I裂解，解离催化亚基 来自两种途径的C3/C5转化酶，并且不受 替代途径激活表面。 CR 1的一种可溶形式，sCR 1 制备缺乏跨膜和胞质结构域的 这些抑制活性的优点。 sCRI至少是 在体外比C4结合蛋白和H更具有抑制作用， 补体激活和组织坏死在体内的模型， 心肌缺血/再灌注损伤 这些研究将被延长 通过确定CRI抑制功能所需的SCR， 制备具有改善的半衰期的可溶性CR 1/IgG构建体， 组织分布和抑制补体依赖性模型， 自身免疫性疾病实验性过敏性重症肌无力 的 补体增强体液免疫应答的能力是由 部分通过B细胞受体，补体受体2型（CR2; CD 21） 其增强mIgM对磷脂酶C（PLC）的激活。 CR2形成a 与CD 19（一种在所有阶段表达的膜蛋白）形成1：1复合物 除了浆细胞外，B细胞发育的细胞是 免疫球蛋白超家族，具有247个延伸的胞质结构域 氨基酸，并在连接后释放细胞内Ca++，所有 生物学中重要的膜成分的特性 B细胞。 在成熟的B细胞中，CR2/CD 19复合物可能代表一种 功能信号转换单元。 拟议的研究将 证明CR2是配体结合亚单位，CD 19是信号 转导亚基的复合物，CD 19利用途径PLC 与mIgM的活化不同，并且CD 19与mIgM的活化偶联， 蛋白质酪氨酸激酶。 通过CR2/CD 19复合物，补体 可以通过对该细胞生物学基本的途径触发B细胞 类型.

Two functions of the complement system related to autoimmune diseases are the induction of an inflammatory response and the augmentation of an immune response. Studies of two complement receptors are proposed that address both functions. A group of plasma and membrane proteins sharing a structural motif inhibit the C3/C5 convertase step of the classical and alternative pathways. One member of this family, complement receptor type 1 (CR1; CD35) normally serves as a receptor but is uniquely suited for complement inhibition. CRI binds bivalently to dimers of C3b and C4b, promotes their cleavage by I, dissociates the catalytic subunits from the C3/C5 convertases of both pathways, and is not restricted by alternative pathway activating surfaces. A soluble form of CR1, sCR1 lacking the transmembrane and cytoplasmic domains was prepared to take advantage of these inhibitory activities. The sCRI was at least 100-fold more inhibitory than C4-binding protein and H in vitro and suppressed complement activation and tissue necrosis in vivo in a model of myocardial ischemia/reperfusion injury. These studies will be extended by determining the SCRs required for the inhibitory functions of CRI, preparing soluble CR1/IgG constructs having improved half-lives and tissue distribution and suppressing a complement-dependent model of autoimmune disease, experimental allergic myasthenia gravis. The capacity of complement to enhance the humoral immune response is mediated in part by the B cell receptor, complement receptor type 2 (CR2; CD21) which augments activation of phospholipase C (PLC) by mIgM. CR2 forms a 1:1 complex with CD19, a membrane protein that is expressed at all stages of B cell development except that of the plasma cell, is a member of the immunoglobulin superfamily, has an extended cytoplasmic domain of 247 amino acids, and releases intracellular Ca++ following ligation, all characteristics of a membrane constituent important in the biology of the B cell. In the mature B cell the CR2/CD19 complex may represent a functional signal transducing unit. The proposed studies will demonstrate that CR2 is a ligand binding subunit and CD19 the signal transducing subunit in the complex, that CD19 utilizes a pathway to PLC activation that is distinct from that of mIgM, and that CD19 is coupled to a protein tyrosine kinase. Through the CR2/CD19 complex, complement may trigger B cells by a pathway fundamental to the biology of this cell type.