Somatic Cell Genetics of Antibody-secreting Cells: Studies of Clonal Diversification and Analysis by Cell Fusion

Abstract

The nature and genetic origin of antibody di-versity was perhaps the most important topic discussed 9 years ago at the Cold Spring Harbor Symposium on Antibodies. The existence of mul-tiple germ-line genes coding for the V region of a given chain was then hotly disputed. It was very soon after that symposium that the existence of at least three nonallelic VK genes in humans be-came firmly established (Milstein 1967; Milstein et al. 1969). Since then, the concept of multiple V genes in the germ line has been generally accepted for most of the types and classes of immunoglob-ulin (Ig) chains in a variety of species (Gally 1973). The germ-line genes, however, do not seem to cover the whole structural Ig diversity. Estimates of the reiteration frequency of V genes by molecular hybridization techniques have been made in recent years. The subject has been reviewed (Rabbitts and Milstein 1976) and is extensively discussed in this volume. The results of these studies generally indicate that somatic events are important contributors to antibody diversity. The way in which somatic diversification is achieved remains a largely speculative subject. Mutation mechanisms in prokaryotes are known in considerable detail, but there is very little docu-mented information about somatic structural gene mutations. It was this lack of information that prompted our studies on the clonal diversification of MOPC-21 cells in culture.