Leder P, Honjo T, Packman S, Swan D, Nau M, Norman B
Proc Natl Acad Sci U S A. 1974 Dec;71(12):5109-15. doi: 10.1073/pnas.71.12.5109.
We have used purified mouse immunoglobulin light chain mRNA and synthetic DNA which is complementary to it to assess the reiteration frequency of gene sequences corresponding to the kappa constant region of the mouse immunoglobulin light chain. These studies indicate that the constant region sequence is represented only two to three times per haploid mouse genome, a finding that rules out a simple stringent germ line mechanism which would require the constant region sequence to be represented hundreds if not thousands of times. Hybridization studies involving (125)I-labeled myeloma light chain mRNA yield interesting results which may eventually permit us to distinguish between the remaining somatic mutation and recombinational germ line hypotheses. These results reveal a major component of relatively unique frequency and a minor component with a reiteration frequency of approximately 30 to 50 copies per haploid genome. As discussed, these results do not permit us to distinguish unambiguously between a germ line model and a type of somatic mutation model that permits germ line genes corresponding to each kappa subgroup. The results do, however, clearly rule out the existence of thousands of variable region sequences so closely related to the MOPC-41 V-region as to permit extensive stable cross-hybridization.
我们使用纯化的小鼠免疫球蛋白轻链mRNA和与之互补的合成DNA,来评估与小鼠免疫球蛋白轻链κ恒定区相对应的基因序列的重复频率。这些研究表明,恒定区序列在每个单倍体小鼠基因组中仅出现两到三次,这一发现排除了一种简单的严格种系机制,该机制要求恒定区序列即使不是出现数千次,也至少要出现数百次。涉及用(125)I标记的骨髓瘤轻链mRNA的杂交研究产生了有趣的结果,这些结果最终可能使我们能够区分剩余的体细胞突变和重组种系假说。这些结果揭示了一个频率相对独特的主要成分和一个在每个单倍体基因组中重复频率约为30至50个拷贝的次要成分。如前所述,这些结果无法让我们明确区分种系模型和一种体细胞突变模型,后者允许对应于每个κ亚组的种系基因存在。然而,这些结果确实清楚地排除了存在数千个与MOPC - 41 V区密切相关、从而允许广泛稳定交叉杂交的可变区序列的可能性。