Antibody Induction and Tolerance

Abstract

Discrete genetic loci, believed to have evolved by gene duplication, control the synthesis of related but not identical polypeptide chains in the hemoglobins (1). Partial gene duplication has been suggested as the mechanism for the evolution of the Hp2 allele in the haptoglobin system (2, 3). Intergenic crossing-over between regions of homology in such related genes has been established in both the haptoglobin (3, 4) and hemoglobin (5) systems. I have suggested (6) comparable intragenic crossing-over may occur somatically in the genes controlling antibody structure and the resulting chromosomal rearrangements could account for variations in the structure of the polypeptides of different antibodies. At time I made no reference to any selective (7) or instructive (8) mechanisms for the induction of antibody responses since the control of antibody structures did not appear to be necessarily coupled with either mechanism for antibody induction. I now propose a hypothesis for antibody induction and the control of tolerance which suggests both selective and instructive stages may participate in the overall process. In developing the hypothesis I have necessarily considered principles and ideas discussed by other writers. Particularly I draw attention to a discussion by Burnet (9) and a paper by Jerne et al. (10) which raise considerable doubt a simple process of clonal selection and subsequent cell division can account for the rapidity of the primary response and the large proportion of responding to a given antigen. Jerne et al. offer several interpretations of their own data, including the ideas cells initially stimulated release a self-replicating RNA which infects a number of of the plasma cell series or that an episomal gene cod-