在小鼠严重综合免疫缺陷中存在的缺陷:信号序列的连接,但在V(D) J重组中没有编码段
M R Lieber1, J E Hesse, S Lewis
1Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Cell
|October 7, 1988
概括
严重综合免疫缺陷 (scid) 的小鼠表现出异常的V(D) J重组. 编码末端连接中的这个缺陷阻止了免疫球蛋白和T细胞受体的产生,解释了免疫缺陷.
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:
- 严重联合免疫缺陷 (SCID) 是一组遗传疾病,其特点是T和B淋巴细胞的严重缺陷.
- V(D) J重组过程对于产生抗原受体的多样性至关重要,包括免疫球蛋白和T细胞受体.
研究的目的:
- 研究V(D) J重组缺陷背后的分子机制.
- 为了确定在scid前B和前T细胞中编码末端连接的失败是否解释了功能性抗原受体的缺失.
主要方法:
- 通过含有V(D) J重组信号序列的等离子体,从Scid小鼠中传染B前和T前细胞系.
- 对回收的等离子体进行分析,以评估信号末端连接和编码末端连接.
- 在重组过程中核酸删除和反转的评估.
主要成果:
- 信号末端在scid细胞中结合在一起,但在约一半的重组剂中出现异常的核酸缺失.
- 在删除和反向V(D) J重组反应中,编码末端都无法连接.
- 观察到编码末端参与了非V (D) J的替代性重组路径.
结论:
- 编码关节形成的失败是V(D) J在scid前B和T细胞中的重组的主要缺陷.
- 这种缺陷足以解释Scid小鼠缺乏免疫球蛋白和T细胞受体表达.
- 了解这种机制可以了解淋巴细胞的发育和免疫系统的功能.
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