Baranov O K, Eppel' M S
Genetika. 1984 Sep;20(9):1397-413.
Repertoire of immunoglobulin paratopes is estimated as at least 10(7)-10(8) per individual. This repertoire is created by the variability of paratope coding VH- and VL-genes. Three events contribute to the necessary diversity of VH- and VL-genes: 1. Sets of germline DNA segments: VH, DH, JH and VL, JL containing genetic information for different parts of V-domains amino acid sequence. 2. Ontogenic rearrangements of these segments resulting in generation and expression of complete VH- and VL-genes. These rearrangements create the third hypervariable region diversity. 3. Succeeding hypermutational process leading to numerous substitutions of single amino acids along the V-domain localized essentially in hypervariable (complementary determining) regions. This process possesses the greatest possibilities for generation of somatic diversity of V-genes. Final VH- and VL-genes diversity reaches the necessary paratope repertoire, due to epigenetic mechanism of heavy and light chains combination in immunoglobulin molecules. Mechanisms of somatic generation of V-genes diversity are interpreted to spring up and be maintained in the course of evolution because of the fact that micro-parasites (viruses and bacteria) have much higher changeability rate than their hosts--highest vertebrates. Since future evolution of micro-parasites cannot be foreseen with the past events as a basis, natural selection of many thousands of germline V-genes fails to bring adaptation of the immune system to changeability of infection agents. Optimal evolution strategy of immunoglobulin gene complex of host species is expected to ensure developing somatic mechanisms. These mechanisms would generate de novo broad and random V-gene variability which is able, through structure diversity of corresponding paratopes, to foresee not only arbitrary micro-parasite, but also any arbitrary antigen not known in phylogenesis.
据估计,每个人的免疫球蛋白互补决定区(paratope)库至少有10^7 - 10^8个。这个库是由编码互补决定区的重链可变区(VH)和轻链可变区(VL)基因的变异性产生的。有三个事件促成了VH和VL基因的必要多样性:1. 种系DNA片段集:VH、DH、JH以及VL、JL,它们包含V结构域氨基酸序列不同部分的遗传信息。2. 这些片段的个体发育重排,导致完整VH和VL基因的产生和表达。这些重排产生了第三个高变区的多样性。3. 随后的高突变过程,导致沿V结构域的单个氨基酸大量替换,主要定位在高变(互补决定)区。这个过程在产生V基因的体细胞多样性方面具有最大的可能性。由于免疫球蛋白分子中重链和轻链组合的表观遗传机制,最终VH和VL基因的多样性达到了必要的互补决定区库。V基因多样性的体细胞产生机制被解释为在进化过程中出现并得以维持,因为微寄生虫(病毒和细菌)的变化率比它们的宿主——高等脊椎动物要高得多。由于无法以过去的事件为基础预测微寄生虫未来的进化,数千种种系V基因的自然选择无法使免疫系统适应感染因子的变化性。宿主物种免疫球蛋白基因复合体的最佳进化策略预计将确保发展体细胞机制。这些机制将从头产生广泛而随机的V基因变异性,通过相应互补决定区的结构多样性,不仅能够预见任意的微寄生虫,还能预见系统发育中未知的任何任意抗原。