Combinatorial events in generation of antibody diversity.

Combinatorial association of immunoglobulin gene elements is the most important process in the creation of extreme diversity of antibody molecules. The recombination of germ-line variable gene elements V, D, and J can potentially generate approximately 6000 variable genes of human heavy chains. As joining of these elements is imprecise and is occurring with nucleotide additions or deletions, the created diversity is in fact much higher. The assembled variable genes can be revised and edited resulting in a change of their affinity and even specificity. Due to somatic hypermutation, the affinity of synthesized antibody increases even more. Another variant of combinatorial recombination is joining of complete variable genes with one of the several constant genes and the formation of various immunoglobulin isotypes with different effector functions but with the same antibody specificity. Consequently, these processes not only develop the antibody repertoire but also solve some other problems of the adaptive immune response.