The generation of antibody diversity.

By their nature, antibody molecules exhibit a wide range of binding specificities. The antigen-binding properties of the antibody reside entirely in the amino-terminal portion of the molecule, termed the variable domain. Structurally, the combining site specificity is determined by the amino-acid residues within 6 short lengths, 3 each in the heavy and light chains, of usually variable sequence. The hypervariability of 2 of these lengths arises from the somatic recombination of short gene segments into a single stretch of mRNA which encodes the entire variable region of 1 polypeptide chain. For example, a V gene segment that codes for most of the variable portion of a light chain, can combine with one of a number of much shorter J gene segments to create the complete variable region gene. In heavy chain genes, a third element, the D gene segment, increases the potential for diversity even further. A mechanism has been proposed by which variability occurs at the point where 2 gene segments join. Thus, a large part of the generation of antibody diversity occurs in the somatic recombination of small genetic elements.