Bentley D L, Rabbitts T H
Cell. 1981 Jun;24(3):613-23. doi: 10.1016/0092-8674(81)90088-x.
To assess the relative contributions of germline versus somatically mutated genes in the human immune system, we have examined the size of the kappa light-chain variable region (V kappa) gene pool. Two cloned kappa subgroup 1 (V kappa 1) gene probes detected the same family of 15 to 20 crosshybridizing restriction fragments in human DNA, whereas flanking region probes detected fewer hybridizing fragments. Most of the hybridizing bands represent single-copy genes, as judged by a "'gene titration" experiment. Furthermore, the number of hybridization bands is a good estimate of the haploid gene number, since we observed little polymorphism of restriction sites in the V kappa locus of eight unrelated people. A cloned V kappa 3 probe hybridized to essentially the same 15--20 genes in human DNA as the V kappa 1 probes. These results strongly suggest that a discrete family of 15--20 genes constitutes a large proportion of the V genes from three of the four V kappa subgroups. The small number of V kappa genes in the human genome supports the idea that somatic mutation plays a major role in the origin of antibody diversity in man.
为了评估种系基因与体细胞突变基因在人类免疫系统中的相对作用，我们检测了κ轻链可变区（Vκ）基因库的大小。两种克隆的κ亚群1（Vκ1）基因探针在人类DNA中检测到相同的15至20个可交叉杂交的限制性片段家族，而侧翼区域探针检测到的杂交片段较少。通过“基因滴定”实验判断，大多数杂交带代表单拷贝基因。此外，杂交带的数量是单倍体基因数量的良好估计，因为我们在八个无关个体的Vκ基因座中观察到限制性位点的多态性很少。一个克隆的Vκ3探针与人类DNA中的15 - 20个基因杂交，与Vκ1探针杂交的基因基本相同。这些结果强烈表明，一个由15 - 20个基因组成的离散家族构成了四个Vκ亚群中三个亚群V基因的很大一部分。人类基因组中Vκ基因数量较少，这支持了体细胞突变在人类抗体多样性起源中起主要作用的观点。
