Jirik F R, Sorge J, Fong S, Heitzmann J G, Curd J G, Chen P P, Goldfien R, Carson D A
Proc Natl Acad Sci U S A. 1986 Apr;83(7):2195-9. doi: 10.1073/pnas.83.7.2195.
The contribution of germ-line variable regions to autoantibody formation in humans is poorly understood. To study the gene structure of a human autoantibody, chronic lymphatic leukemia (CLL) cells from a patient with an IgM anti-IgG (rheumatoid factor, RF) paraprotein were utilized. The rearranged immunoglobulin gene encoding the kappa light chain for the RF was cloned, and the nucleic acid sequence of its variable region was determined. As demonstrated by Southern blot analysis using a kappa joining-region probe, the CLL cells, stable CLL-WIL2-729-HF2 RF-secreting hybridomas, and the cloned light-chain gene all had an identical restriction fragment containing the rearranged light-chain gene. The CLL RF light chains reacted weakly with an antipeptide antibody against a primary structure-dependent idiotype present on the light chains of the majority of IgM RF paraproteins. The nucleotide and predicted amino acid sequences of the CLL light-chain gene place it in the kappa III variable-region subgroup, and a comparison to known RF paraproteins reveals marked homology to the light-chain amino acid sequence of the IgM RF paraprotein Pom. Both Pom and the CLL light chain appear to identify a second kappa III gene or gene group that is able to encode RF paraprotein light chains.
生殖系可变区对人类自身抗体形成的贡献目前了解甚少。为了研究一种人类自身抗体的基因结构,利用了一名患有IgM抗IgG(类风湿因子,RF)副蛋白血症患者的慢性淋巴细胞白血病(CLL)细胞。克隆了编码RF κ轻链的重排免疫球蛋白基因,并测定了其可变区的核酸序列。用κ连接区探针进行的Southern印迹分析表明,CLL细胞、稳定分泌CLL-WIL2-729-HF2 RF的杂交瘤以及克隆的轻链基因都有一个相同的包含重排轻链基因的限制性片段。CLL RF轻链与针对大多数IgM RF副蛋白轻链上存在的依赖一级结构的独特型的抗肽抗体反应较弱。CLL轻链基因的核苷酸和预测的氨基酸序列将其归入κIII可变区亚组,与已知的RF副蛋白进行比较发现,它与IgM RF副蛋白Pom的轻链氨基酸序列有明显的同源性。Pom和CLL轻链似乎都鉴定出了第二个能够编码RF副蛋白轻链的κIII基因或基因组。