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免疫球蛋白基因转换还是高突变:这就是问题所在。

Immunoglobulin gene conversion or hypermutation: that's the question.

作者信息

Buerstedde Jean-Marie, Arakawa Hiroshi

机构信息

GSF, Institute for Molecular Radiobiology, Ingolstaedter Landstr. 1, D-85764 Neuherberg-Munich, Germany.

出版信息

Subcell Biochem. 2006;40:11-24. doi: 10.1007/978-1-4020-4896-8_2.

Abstract

Chicken B cells develop their primary immunoglobulin (Ig) gene repertoire by pseudogene templated gene conversion within the bursa of Fabricius. The DT40 cell line is derived from bursal B cells and continues to diversify its rearranged Ig light chain in cell culture. Ig gene conversion of DT40 requires expression of the AID gene which was earlier shown to be needed for Ig hypermutation and switch recombination in mammalian B cells. Interestingly, Ig hypermutation can be induced in DT40, if Ig gene conversion is blocked by the disruption of RAD51 paralog genes, the deletion of the nearby pseudogene locus or the disruption of the UNG gene. The ease of gene targeting and the compactness of the chicken Ig light chain locus makes DT40 an ideal model to study the molecular mechanism of AID induced gene conversion and hypermutation.

摘要

鸡B细胞通过法氏囊内假基因模板化的基因转换来形成其初级免疫球蛋白(Ig)基因库。DT40细胞系源自法氏囊B细胞,并在细胞培养中继续使其重排的Ig轻链多样化。DT40的Ig基因转换需要AID基因的表达,先前已证明该基因是哺乳动物B细胞中Ig高突变和类别转换重组所必需的。有趣的是,如果通过RAD51旁系同源基因的破坏、附近假基因位点的缺失或UNG基因的破坏来阻断Ig基因转换,DT40中可诱导Ig高突变。基因靶向的便利性和鸡Ig轻链基因座的紧凑性使DT40成为研究AID诱导的基因转换和高突变分子机制的理想模型。

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