Molecular basis of generation of antibody diversity
Answers
Answer:
Three theories have been put forth to explain antibody diversity, which allows B cells to generate an antibody repertoire capable of reacting with a wide range of antigens: (1) The germ-line theory postulates that separate genes exist for each antibody molecule and that the antibody repertoire is largely inherited. (2) The deoxyribonucleic acid (DNA) rearrangement theory proposes that a limited number of genes undergo genetic rearrangements to create antibody populations. (3) Finally, the somatic mutation theory proposes that a limited number of inherited genes undergo mutations to general antibody repertoires. In vivo and in vitro studies have demonstrated that both the DNA rearrangement theory and the somatic mutation theory provide the most plausible explanations for antibody diversity.
Antibodies are encoded by different germ-line genetic loci. Variable (V) region, joining (J) region, and constant (C) region gene products are assembled into a functional antibody. Variable portion genes (V) code for amino acids that constitute the framework regions of the variable region, and three hypervariable complementarity-determining regions (CDR1, CDR2, and CDR3). The hypervariable regions form the three-dimensional antigen-binding pocket. Antibody specificity is determined by the specific amino acid sequences in CDR3. The joining (J) segment is, in reality, part of the V region and provides some of the framework for the antigen-binding pocket. Only heavy chains have an additional diversity (D) gene.
Antibody diversity is generated from the large number of V, J, D, and C genes available for recombination. Light-chain loci have 30 to 35 genes encoding for the variable (VL) regions (Table 10-1). Five to seven genes code for JL segments in kappa (κ) or lambda (λ) light chains, respectively. Lambda and kappa light chains have one highly conserved constant region.