Vertebrate organisms possess a large and diverse repertoire ofantibody variable regions. A number of different genetic mechanismshave been proposed to account for immunoglobulin variable (V) regiondiversity, including multiple germline genes, somatic mutation,somatic recombination, and multiple small gene segments which arejoined to form a complete variable region gene segment. Analyses ofvariable region amino acid sequences demonstrate the relative contributionof each of these mechanisms to antibody diversity.
Twenty-four VK21 chains have been examined. They suggest that thekappa chain variable region is encoded in two separate gene segments:VK and JK which are rearranged and joined during B cell differentiation.Diversification of the N terminus of the JK segment occurs as a consequence of VK-JK joining and has been explained by a site-specificrecombination model. The amino acid sequence data are consistent withthe existence of a minimum of six VK and five JK germline gene segments.Possible cases of somatic mutation are also observed. These conclusionsare supported by nucleic acid sequence analyses performed byothers.
Complete variable region amino acid sequences have been determinedfor twenty-one heavy chains from dextran binding antibodies. Thesesequences suggest that the heavy chain variable region is encoded bythree gene segments: VH, D, and JH. Nucleic acid sequence analysesare consistent with this conclusion. The existence of a minimum oftwo VH and four JH germline gene segments is suggested by thesesequences. Possible examples of somatic mutation of VH and JH genesegments have also been found. Diversification of the N-terminal residueof the JH segment may occur as a consequence of D-JH joining by amechanism analogous to that observed in kappa chains. Although comprisedof only two residues, the D segment is the most diverse portionof dextran binding heavy chains.
Combinatorial joining of VK and JK gene segments and VH, D, andJH gene segments contributes significantly to antibody diversity.
Precise molecular locations of idiotypic determinants can beestablished in the dextran heavy chains. A cross-reactive idiotypicdeterminant (IdX) is located in the second hypervariable region of theVH segment. Individual idiotypic determinants (IdIs) correspond toparticular D segments.
