Human immunoglobulin variable region genes—DNA sequences of two Vκ genes and a pseudogene
Human immunoglobulin variable region genes—DNA sequences of two Vκ genes and a pseudogene
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人免疫球蛋白可变区基因——两个Vκ基因和一个假基因的DNA序列
作者：
D. Bentley;T. Rabbitts
在分子水平上对免疫球蛋白基因的研究可以帮助我们阐明抗体多样性的起源。对小鼠免疫球蛋白基因结构的研究表明，轻链由三个基因片段编码：编码恒定区的C基因和编码可变区的V和J基因。在产生抗体的细胞中，V和J基因结合在一起形成完整的免疫球蛋白基因1，2。没有关于人轻链可变区基因结构的数据，但已经对超过150种人κ轻链蛋白的可变区进行了测序，它们包括四个不同的亚组3 - 5。本文报道了从人胎肝DNA中分离的三个人κ可变区（V κ）基因的全序列。序列表明，编码亚组I蛋白的两个非等位基因在编码区和非编码区具有超过90%的核苷酸同源性。这些人类基因与小鼠V κ基因的两个完整DNA序列的比较6，7表明，V κ基因结构在两个物种之间高度保守，这表明V κ基因在人类淋巴细胞分化期间通过与小鼠非常相似的机制重排8，9。还描述了缺陷性V κ基因的序列-该基因由于其序列中的取代、缺失和插入而不能编码功能性免疫球蛋白。它类似于珠蛋白11 - 13和爪蟾5S RNA 14的假基因10。
The study of immunoglobulin genes at the molecular level can allow us to elucidate the origin of antibody diversity. Investigations of immunoglobulin gene structure in the mouse have shown that light chains are encoded by three gene segments: the C gene encoding the constant region and the V and J genes encoding the variable region. In antibody-producing cells the V and J genes join together to create a complete immunoglobulin gene1,2. No data are available on the structure of human light chain variable region genes, but the variable regions of over 150 human κ light chain proteins have been sequenced and they comprise four distinct subgroups3–5. Here we report the complete DNA sequences of three human κ variable region (Vκ) genes isolated from fetal liver DNA. The sequences demonstrate that two non-allelic genes encoding subgroup I proteins have more than 90% nucleotide homology in both coding and non-coding regions. Comparison of these human genes with two complete DNA sequences of mouse Vκ genes6,7 shows that Vκ gene structure is highly conserved between the two species, which suggests that Vκ genes rearrange during the differentiation of human lymphocytes by a very similar mechanism to that in the mouse8,9. The sequence of a defective Vκ gene is also described—this gene is unable to code for a functional immunoglobulin due to substitutions, deletions and insertions in its sequence. It is analogous to the pseudogenes10 of globin11–13 and Xenopus 5S RNA14.