Regulation of CR2/CD21 Expression and Activation

小鼠CD21/Cr2基因编码两种与获得最佳免疫有关的蛋白质 回应。CD21途径包括B细胞存活和最佳激活的信号，以及 位于脾生发中心的滤泡树突状细胞(FDC)产生的天然抗原。的表达方式 小鼠CD21受到严格控制。这些蛋白质是在B细胞分化的特定阶段发现的 一旦它们在脾内就位，FDC就会表达它们。 这项相互竞争的申请建议继续我们对CD21基因控制机制的分析 以及CD21蛋白在产生适当的免疫反应中的功能。我们有 证实了启动子和内含子元件调控CD21基因。我们建议继续我们的 分析CD21的转录控制，结合另外两个基因的比较分析， CD19和CD23，在B细胞分化的相似时间表达。我们还将继续我们的 对CD21内含子控制区基因工程缺失的突变小鼠品系的检查。这些 分析还包括疱疹病毒转录激活物诱导CD21和CD23的作用 表达，以及这种过度表达对免疫反应的影响。 我们对CD21蛋白功能的分析将集中在CD21蛋白作为 补体受体增强获得性和先天免疫反应 免疫球蛋白亚型。我们还将分析各种基因产物的作用，这些基因产物表达的 CD21缺陷动物在免疫激活过程中发生严重变化。 产生适当的免疫反应对个体的健康至关重要。CD21 蛋白质跨越获得性和先天免疫反应领域，因此它们的操纵可以 影响对感染的即时反应以及免疫学更长期的后果 记忆。

The murine CD21/Cr2 gene encodes two proteins implicated in the acquisition of an optimal immune response. The CD21 pathway includes signals for B cell survival and optimal activation, and presentation of native antigen by follicular dendritic cells (FDC) in the germinal centers of the spleen. The expression of murine CD21 is tightly controlled. The proteins are found on B cells during specific stages of differentiation and are expressed by FDC once they have taken up their position within the spleen. This competing application proposes to continue our analysis of the mechanism of CD21 gene control and the functions of the CD21 proteins in the generation of an appropriate immune response. We have demonstrated that promoter and intronic elements regulate the CD21 gene. We propose to continue our analysis of the transcriptional control of CD21, incorporating the comparative analysis of two other genes, CD19 and CD23, that are expressed at similar times of B cell differentiation. We will also continue our examination of a mutant mouse line with an engineered deletion of the CD21 intronic control region. These analyses also include the role of transcriptional activators from herpes virus that induce CD21 and CD23 expression, and the effect of such over expression on the immune response. Our analysis of the function of the CD21 proteins will focus upon the role of the CD21 proteins as complement receptors enhancing both the acquired and innate immune responses including the generation of the immunoglobulin isotypes. We will also analyze the role of various gene products whose expression is critically altered in CD21 deficient animals during immune activation. The generation of an appropriate immune response is critical to the health of the individual. The CD21 proteins straddle the fields of acquired and innate immune responses such that their manipulation could influence immediate responses to an infection as well as the more long term consequences of immunologic memory.