[Genetic bases of antibody diversity]

Abstract

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.