MOLECULAR REQUIREMENTS FOR ANTIBODY CLASS SWITCHING

描述（改编自研究者摘要）：我们正在调查 免疫球蛋白重链恒定的作用机制和调节 区域基因开关重组酶作为B细胞生理学的功能， 发展转换底物逆转录病毒（SSR）将被引入到 成熟鼠和人B淋巴细胞的培养物，纯化的人B亚群 细胞和鼠前B细胞，以评估活化、调节和 开关重组酶活性的发育时间。模型B细胞系 将采用对CD 40和细胞因子信号传导敏感的细胞因子来区分 启动和/或增强 转换重组酶活性。将进行灵敏的PCR检测， 当这些细胞暴露于CD 40时SSR重组的结果 受体信号传导、细胞因子和已知影响内源性 抗体类别转换。含有CH位点调控元件的SSR和RNA 成熟信号将用于确定它们在以下方面的假定作用： 靶向CH基因区段用于开关重组。

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.