在编辑和切换外围B细胞中促进转位的机制
Jing H Wang1, Monica Gostissa, Catherine T Yan
1Howard Hughes Medical Institute, USA.
Nature
|July 10, 2009
概括
外围B细胞可以经历二次V(D) J重组,导致DNA断裂和转位. 这项研究揭示了促进瘤中反复转位的机制因素.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 变量,多样性和连接 (V,D,J) 重组和类切换重组 (CSR) 对免疫球蛋白基因组合和功能至关重要.
- 两种V(D) J和CSR都依赖于通过非同类末端连接 (NHEJ) 修复的DNA双链断裂 (DSB).
- 这些过程中的错误可能导致染色体转位,这与B细胞淋巴瘤有关.
研究的目的:
- 为了调查V(D) J重组在外围B细胞中的有争议的发生情况.
- 探索V(D) J重组与CSR在产生转移方面的潜在合作.
- 确定导致瘤中反复转位的机制因素.
主要方法:
- 对激活的,缺乏NHEJ的骨B细胞的分析.
- 在Lambda IgL位点 (Igl) 检测与V(D) J重组相关的断裂.
- 评估与CSR相关的IgH断裂和转位形成.
- 调查IGH-IGL和IGH-c-myc的同定位.
- 引入c-myc DSB来研究转移促进.
主要成果:
- 缺少NHEJ的骨B细胞在IGL积累V(D) J相关的断裂,在IGH积累CSR相关的断裂.
- Igl 和 Igh 断裂经常结合在一起形成转位,通常与 Igh-Igl 共定位有关.
- 观察到IGH和c-myc的同定位,c-myc的DSB强有力的促进IGH-c-myc的转移.
- 有证据表明,外围B细胞试图进行二次V(D) J重组.
结论:
- 外围B细胞可以经历二次V(D) J重组.
- 机械因素有助于瘤中反复转位的形成.
- 这项研究阐明了V(D) J重组在外围B细胞中的作用及其与瘤转位的联系.
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