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针对抗体基因的突变结果的序列内在机制

Leng-Siew Yeap¹, Joyce K Hwang¹, Zhou Du¹

¹Howard Hughes Medical Institute, Program in Cellular and Molecular Medicine at Boston Children's Hospital, and Department of Genetics, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

|November 20, 2015

概括

这项研究显示,酶AID对抗体突变和类交换的DNA具有相似的向,这表明有共同的机制. 它还表明抗体基因位置不是B细胞突变的唯一特征.

科学领域:

免疫学
分子生物学
遗传学

背景情况:

激活的B淋巴细胞利用激活诱导的胺酶 (AID) 进行关键的免疫过程.
艾滋病驱动体变异 (SHM) 在抗体变量 (V) 异构体中,以在生殖中心 (GC) 中成熟.
此外,AID还会诱导IgH切换 (S) 区域的DNA断裂,从而促进类切换重组 (CSR).

研究的目的:

研究B淋巴细胞中的AID向机制和DNA修饰过程.
通过研究AID对乘客序列的作用来阐明SHM和CSR之间的关系.
与其他DNA区域相比,确定V外因子位置是否是AID针对SHM的唯一目标.

主要方法:

开发一种在体内测试,以追踪替代V外因子的AID向.
对V exon和S区域乘客的AID突变频率的分析.
在GC B细胞内的各种非Ig乘客序列中评估AID突变水平.

主要成果:

AID以相似频率针对V地区和S地区的SHM热点旅客.
这一过程本质上产生了删除,支持了企业社会责任的共享机制.
AID在GCB细胞中的非Ig乘客序列中发生突变,其水平与V外因子相似,从而挑战了V外因子特权的概念.
在基于亲和力的选择之前,皮耶补丁GCB细胞积累了高度突变的V外因子.

结论:

身体突变和类交换重组可能具有由AID启动的共同的基底DNA修饰机制.
对于SHM来说,V外基因不是唯一的"特权";其他DNA区域在GCB细胞中以类似的速度被AID突变.
皮耶补丁GCB细胞中存在大量预先选择的,高度突变的抗体V外形,影响了对抗体多样化的理解.

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