MOLECULAR REQUIREMENTS FOR ANTIBODY CLASS SWITCHING

描述(改编自调查人员摘要)：我们正在调查 免疫球蛋白重链常数的作用机制及其调节 区域基因开关重组酶与B细胞生理和功能的关系 发展。开关底物逆转录病毒(SSR)将引入 培养成熟的小鼠和人B淋巴细胞，纯化的人B细胞亚群 细胞和小鼠前B细胞的激活、调节和 开关重组酶活性的发育时序。模型B细胞系 响应CD40和细胞因子的信号将被用来区分 在启动和/或增强细胞外信号之间 开关重组酶活力。将进行敏感的聚合酶链式反应分析以揭示 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、细胞因子和树突状细胞 抗体类别切换。含有CH基因调控元件和RNA的SSR 成熟信号将被用来确定它们在其中的假定作用(S) 以CH基因片段为靶点进行开关重组。

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.