BIOLOGY AND BIOCHEMISTRY OF THE HUMAN C3B RECEPTOR

与自身免疫性疾病相关的补体系统的两个功能是 炎症反应的诱导和血管紧张素转换酶的增强 免疫反应。建议对两种补体受体进行研究 解决这两个功能。一组共享的质膜蛋白 结构基序抑制C3/C5转换酶步骤 另一条路。补体受体是这个家族的成员之一。 1型(CR1；CD35)通常作为受体发挥作用，但它是唯一适合的 用来抑制补体。CRI与C3b和C3b的二聚体以二价结合 C4b通过I促进它们的切割，解离催化亚基 来自两个途径的C3/C5转换酶，并且不受 另一种途径激活表面。CR1的可溶性形式，sCR1 缺乏跨膜和细胞质结构域的准备要采取 这些抑制活性的优势。SCRI至少是100倍 比C4结合蛋白和H更强的体外抑制和抑制 补体活化与体内组织坏死 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， 制备具有改善半衰期和可溶性CR1/Ig G的载体 补体依赖模型的组织分布及抑制作用 自身免疫性疾病，实验性过敏性重症肌无力。这个 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；CD21) 增强mIgM对磷脂酶C(PLC)的激活作用。CR2构成一个 与CD19的1：1复合体，CD19是一种在所有阶段都表达的膜蛋白 除了浆细胞外，是B细胞发育的一员 免疫球蛋白超家族，具有扩展的胞浆结构域247 氨基酸，并在结扎后释放细胞内钙离子，所有 一种在水母细胞生物学中很重要的膜成分的特性 B细胞。在成熟的B细胞中，CR2/CD19复合体可能代表一个 功能信号转换单元。拟议的研究将 证明CR2是配体结合亚基，CD19是信号 在复合体中的转导亚单位，CD19利用一条途径到达PLC 不同于mIgM的激活，CD19是偶联的 一种蛋白酪氨酸激酶。通过CR2/CD19复合体，补体 可能通过一条对B细胞生物学基本的途径来触发B细胞 打字。

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.