迪克尔切除会影响B淋巴细胞系的抗体多样性和细胞存活率
Sergei B Koralov1, Stefan A Muljo, Gunther R Galler
1Immune Disease Institute and Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
在B淋巴细胞发育中的Dicer酶切除阻断了前B细胞过渡到前B细胞过渡. 这部分是由于增加了Bim,一种亲的分子,可以通过准Bim或增强Bcl-2来挽救.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 迪克尔酶对于微RNA (miRNA) 处理至关重要.
- B 淋巴细胞的发育涉及复杂的基因调节.
- 对Dicer的失调会影响细胞过程和发育.
研究的目的:
- 研究Dicer-依赖机制在B淋巴细胞发育中的作用.
- 为了确定受Dicer剥离影响的分子通路,在B细胞祖先中.
- 评估Dicer缺乏对V(D) J重组的影响.
主要方法:
- 在早期的B细胞原始体中,Dicer酶的剥离.
- 基因表达造型,以识别高调的基因.
- 免疫球蛋白重量 (IgH) 和卡帕链位点重排的分析.
- 评估无菌转录和N序列添加.
主要成果:
- 迪塞尔切除导致了在前B细胞阶段的前B细胞阶段的发育阻断.
- 观察到一个miR-17大约92个签名,与proapoptotic分子Bim.上调.
- 通过切除Bim或过度表达Bcl-2,可以部分挽救B细胞的发育.
- 观察到完整的Ig基因重新排列,但与增加的无菌转录和N序列添加.
结论:
- 对于正常的B淋巴细胞发育,Dicer-依赖的控制是必不可少的.
- 由miR-17约92调节的亲细胞分子Bim在Dicer缺乏B细胞中起着关键作用.
- 迪克尔缺乏影响V(D) J重组通过终端脱氧核酸转移酶的放松转录.
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