ABSTRACT
Human immunoglobulin (Ig) molecules are coded by three unlinked gene families: two for light (L) chains located on chromosomes 2 (k chains) and 22 (l chains), and one for heavy (H) chains located on chromosome 14. As mentioned in the preceding chapters, each individual is able to produce billions of antibody molecules with different antigenic specificities, and this diversity corresponds to the extreme heterogeneity of the variable (V) regions in those antibody molecules, implying that each individual must possess a large number of structural genes for Ig chains. The allotypic determinants on the constant (C) region (see following discussion), on the other hand, segregate as a single Mendelian trait, suggesting that there may be only one gene for each of the several Ig chain C regions. To reconcile these seemingly contradictory observations, Dreyer and Bennet, in 1965, proposed that two separate genes that are brought together by a translocation event during lymphocyte development encode the V and C regions. Employing recombinant DNA technology, Hozumi and Tonegawa, in 1976, obtained conclusive proof of this hypothesis (for his seminal studies, Tonegawa was awarded the 1987 Nobel prize in Medicine and Physiology).
