MOLECULAR REQUIREMENTS FOR ANTIBODY CLASS SWITCHING

抗体类别转换的分子要求

• 批准号: 6385372
• 负责人: KENNETH B MARCU
• 金额: $ 26.38万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6385372
• 关键词: B lymphocyte; CD40 molecule; Retroviridae; antibody formation; biological signal transduction; cell differentiation; enzyme activity; fusion gene; gene expression; gene rearrangement; immunoglobulin genes; laboratory mouse; molecular cloning; nucleic acid sequence; polymerase chain reaction; recombinase; tissue /cell culture; transcription factor; transfection

DESCRIPTION (Adapted from Investigator's Abstract): We are investigating the mechanisms of action and regulation of the immunoglobulin heavy chain constant region gene switch recombinase as a function of B cell physiology and development. Switch substrate retroviruses (SSRs) will be introduced into cultures of mature murine and human B lymphocytes, purified subsets of human B cells and murine pre-B cells to assess the activation, regulation and developmental timing of switch-recombinase activity. Model B cell lines responsive to CD40 and cytokine signaling will be employed to discriminate between extracellular signals that initiate and/or potentiate switch-recombinase activity. Sensitive PCR assays will be performed to reveal the consequences for SSR recombination as these cells are exposed to CD40 receptor signaling, cytokines, and dendritic cells known to affect endogenous antibody class switching. SSR harboring CH locus regulatory elements and RNA maturation signals will be employed to determine their putative role(s) in targeting CH gene segments for switch recombination.

描述（改编自研究者摘要）：我们正在调查 免疫球蛋白重链常数的作用机制和调节 区域基因开关重组酶作为 B 细胞生理学的功能和 发展。开关底物逆转录病毒（SSR）将被引入 成熟鼠和人 B 淋巴细胞培养物、纯化的人 B 淋巴细胞亚群 细胞和小鼠前 B 细胞来评估激活、调节和 开关重组酶活性的发育时间。 B型细胞系 对 CD40 和细胞因子信号传导作出反应将用于区分 启动和/或增强的细胞外信号之间 开关重组酶活性。将进行灵敏的 PCR 检测以揭示 当这些细胞暴露于 CD40 时 SSR 重组的后果 已知影响内源性的受体信号传导、细胞因子和树突状细胞 抗体类别转换。 SSR 含有 CH 位点调控元件和 RNA 成熟信号将被用来确定它们在 针对 CH 基因片段进行开关重组。