SOMATIC CELL GENETICS OF IG GENES

IG 基因的体细胞遗传学

• 批准号: 2089980
• 负责人: MATTHEW D SCHARFF
• 金额: $ 100.95万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2089980
• 关键词: Cryptococcus neoformans; antibody formation; autoantibody; clone cells; gene mutation; gene rearrangement; genetically modified animals; immunogenetics; immunoglobulin genes; immunoglobulin isotypes; laboratory mouse; molecular genetics; mycosis; neutralizing antibody; transfection; virus diseases

We will investigate the molecular mechanisms responsible for the tissue specific and developmentally regulated hypermutation of immunoglobulin variable region genes. This will be done by introducing manipulated transfected genes into: 1) B cell lines whose endogenous immunoglobulin genes are constitutively unstable or whose instability is triggered by T cells and 2) transgenic mice. We will also study the role and impact of V region mutations and isotype switching on the immune response to viruses and fungi in normal mice and on the production of autoantibodies in lupus prone autoimmune mice. We will study the role of affinity and avidity in targeting to a model tumor system. We will use the insight gained from these studies to generate antibodies that can be passively administered to protect against HIV and cryptococcus infections and to target to drug resistant tumors.

我们将研究负责组织的分子机制 免疫球蛋白的特定和发育调节的超数 可变区域基因。 这将通过引入操纵来完成 将基因转染为：1）内源性免疫球蛋白的B细胞系 基因是组成型不稳定的，或者其不稳定是由T触发的 细胞和2）转基因小鼠。 我们还将研究V的作用和影响 区域突变和同种型开关对病毒的免疫反应 和真菌在正常小鼠和狼疮中的自身抗体产生 俯卧的自身免疫小鼠。 我们将研究亲和力和亲和力在 靶向模型肿瘤系统。 我们将利用从中获得的见解 这些研究以生成可以被动地给药的抗体 预防艾滋病毒和加密环球感染并靶向药物 抗性肿瘤。