REGULATION OF CR2/CD21 EXPRESSION AND ACTIVATION

描述(申请人摘要)：小鼠CD21/Cr2基因编码两个 蛋白质被证明是获得最佳免疫的关键 回应。长期以来被认为是补体携带的吞噬细胞受体 免疫复合体，CD21途径现在包括B细胞生存和 毛囊树突状细胞对天然抗原的最佳激活和递呈 脾生发中心的细胞(FDC)。小鼠基因的表达 CD21受到严格控制。这些蛋白质只在B细胞中发现 在特定的分化阶段，一旦这些细胞被FDC表达 已经在脾内占据了它们的位置。 这项相互竞争的申请建议继续进行实验室分析 CD21基因调控的机制，并启动一个新的项目进行剖析 受体激活(或失活)的转录途径 结扎术。我们认为CD21基因的转录受一种 一组转录因子，存在于所有淋巴细胞中，并且 T细胞缺乏表达是由于(1)一个位点的存在 T细胞特异性的组蛋白去乙酰基酶，或(2)位点特异性的B细胞 特异组蛋白乙酰基酶。已发表的和初步的数据支持DNA 可获得性作为淋巴细胞CD21表达的主要决定因素。在……里面 提出了活体同源重组实验，以剖析其作用。 B细胞CD21表达调控的关键位点 分化和FDC。 需要检验的第二个主要假设是B细胞通过CD21激活 连接，加上或减少表面免疫球蛋白的激活，导致一条途径 直接影响B细胞状态的转录调控 分化和激活。使用新的基因分析方法，我们 建议充分描述这些转录途径的表达 (抑郁症)已知的和新的基因。对这些途径的阐明将导致 通过这样的激活手段可以在不适当的时候最小化，或者强调 当需要产生最佳的B细胞应答时。

DESCRIPTION (Applicant's Abstract): The murine CD21/Cr2 gene encodes two proteins demonstrated to be critical in the acquisition of an optimal immune response. Long considered as a phagocytic receptor for Complement-bearing immune complexes, the CD21 pathway now 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 only found on B-cells during a specific stage of differentiation, and are expressed by FDC once these cells have taken up their position within the spleen. This competing application proposes to continue the laboratories analysis of the mechanism of CD21 gene control, and to initiate a new project to dissect the transcriptional pathways that are activated (or inactivated) upon receptor ligation. We propose that the transcription of the CD21 gene is regulated by a set of transcription factors that are present in all lymphocytes and that the lack of expression by T-cells is due to either (1) the presence of a site specific, T-cell specific histone deacetylase, or (2) a site specific, B-cell specific histone acetylase. Published and preliminary data supports DNA accessibility as a primary determinant of CD21 expression in lymphocytes. In vivohomologous recombination experiments are proposed to dissect the role of key regulatory sites in the control of CD21 expression during B-cell differentiation and by FDC. The second major hypothesis to be tested is that B-cell activation via CD21 ligation, plus or minus surface Ig activation, leads to a pathway of transcriptional control that directly influences the state of B-cell differentiation and activation. Using novel gene analysis approaches, we propose to fully characterize these transcriptional pathways for the expression (depression) of known and novel genes. Elucidation of these pathways will lead to means by such activation can be minimized when inappropriate, or accentuated when required for the generation of an optimal B-cell response.