Regulation of CR2/CD21 Expression and Activation

CR2/CD21 表达和激活的调节

• 批准号: 7880369
• 负责人: John Weis
• 金额: $ 1.3万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-11 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880369
• 关键词: Animals; Antigens; B cell differentiation; B-Lymphocyte Subsets; B-Lymphocytes; Binding; Biological Assay; Biological Models; CD19 gene; Cell Survival; Cells; Complement 3d Receptors; Complement Receptor; Defect; Elements; Engineering; Environment; Follicular Dendritic Cells; Generations; Genes; Goals; Health; Herpesviridae; Immune; Immune response; Immunoglobulin Isotypes; Immunologic Memory; Individual; Infection; Inflammation Mediators; Ligand Binding; Mediator of activation protein; Molecular; Mus; Mutant Strains Mice; Mutation; Pathway interactions; Population; Positioning Attribute; Proteins; Receptor Signaling; Regulation; Regulator Genes; Regulatory Element; Role; Signal Pathway; Signal Transduction; Site; Spleen; Staging; Structure of germinal center of lymph node; Time; Transcription Coactivator; Transcriptional Regulation; Virus Diseases; comparative; depressed; design; novel; promoter; receptor; research study; response; transcription factor

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.

鼠 CD21/Cr2 基因编码两种与获得最佳免疫有关的蛋白质 回复。 CD21 通路包括 B 细胞存活和最佳激活的信号，以及 脾脏生发中心的滤泡树突状细胞（FDC）产生天然抗原。的表达式为 鼠 CD21 受到严格控制。这些蛋白质存在于特定分化阶段的 B 细胞上 一旦它们在脾脏中就位，FDC 就会表达出来。 这项竞争性申请建议继续我们对 CD21 基因控制机制的分析 以及 CD21 蛋白在产生适当免疫反应中的功能。我们有 证明启动子和内含子元件调节 CD21 基因。我们建议继续我们的 CD21的转录控制分析，结合其他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。我们也将继续我们的 对 CD21 内含子控制区进行工程删除的突变小鼠系的检查。这些 分析还包括诱导 CD21 和 CD23 的疱疹病毒转录激活剂的作用 表达，以及这种过度表达对免疫反应的影响。 我们对 CD21 蛋白功能的分析将重点关注 CD21 蛋白的作用： 补体受体增强获得性和先天性免疫反应，包括生成 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 CD21 缺陷动物在免疫激活过程中发生了严重改变。 产生适当的免疫反应对于个体的健康至关重要。 CD21 蛋白质跨越获得性和先天性免疫反应的领域，因此它们的操纵可以 影响对感染的即时反应以及免疫学的更长期后果 记忆。