Regulation of CR2/CD21 Expression and Activation

鼠CD 21/Cr2基因编码两种与获得最佳免疫相关的蛋白质 反应CD 21途径包括B细胞存活和最佳活化的信号，以及CD 21的呈递。 脾脏生发中心的滤泡树突状细胞（FDC）产生的天然抗原。的表达 鼠CD 21受到严格控制。这些蛋白质在分化的特定阶段存在于B细胞上 并且一旦它们在脾脏内占据了它们的位置就由FDC表达。 这一竞争性申请建议继续我们对CD 21基因控制机制的分析， 以及CD 21蛋白在产生适当的免疫应答中的功能。我们有 表明启动子和内含子元件调节CD 21基因。我们建议继续我们的 分析CD 21的转录控制，结合两个其他基因的比较分析， CD 19和CD 23，它们在B细胞分化的相似时间表达。我们还将继续 检查具有CD 21内含子控制区的工程化缺失的突变小鼠系。这些 分析还包括来自疱疹病毒的转录激活因子诱导CD 21和CD 23的作用 表达，以及这种过表达对免疫应答的影响。 我们对CD 21蛋白功能的分析将集中在CD 21蛋白的作用， 补体受体增强获得性和先天性免疫应答， 免疫球蛋白同种型我们还将分析各种基因产物的作用，这些基因产物的表达是 在免疫激活期间，CD 21缺陷动物中的严重改变。 产生适当的免疫反应对个体的健康至关重要。CD 21 蛋白质横跨获得性和先天性免疫反应的领域， 影响对感染的即时反应以及免疫系统的更长期后果。 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.