Origin of immunoglobulin isotype switching.-猫眼课题宝

DOI：

10.1016/j.cub.2012.03.060

发表时间：

2012-05-22

期刊：

Current biology : CB

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Zhu C;Lee V;Finn A;Senger K;Zarrin AA;Du Pasquier L;Hsu E

来源链接：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3360817/?report=classic

From humans to frogs, immunoglobulin class switching introduces different effector functions to antibodies through an intrachromsomal DNA recombination process at the heavy chain locus. Although there are two conventional antibody classes (IgM, IgW) in sharks, their heavy chains are encoded by 20 to >100 miniloci. These representatives of the earliest jawed vertebrates possess a primordial immunoglobulin gene organization where each gene cluster is autonomous and contains a few rearranging gene segments (VH-D1-D2-JH) with one constant region, μ or ω. V(D)J rearrangement always takes place within the μ cluster, but here we show that the VDJ can be expressed with constant regions from different clusters, although IgH genes are spatially distant, at >120 kb. Moreover, reciprocal exchanges take place between Igω and Igμ genes. Switching is augmented with deliberate immunization and is concomitant with somatic hypermutation activity. Since switching occurs independently of the partners’ linkage position, some events involve transchromosomal recombination. The switch sites consist of direct joins between two genes in the 3′ intron flanking JH. Our data are consistent with a mechanism of cutting/joining of distal DNA lesions initiated by activation-induced cytidine deaminase (AID), in the absence of mammalian-type switch regions. We suggest that, in shark, with its many autonomous IgH targeted by programmed DNA breakage, factors predisposing broken DNA ends to translocate configured the earliest version of class switch recombination.