Chapter 6 - The Clonal Selection Theory of Antibody Formation

Abstract

The clonal selection theory of antibody formation is the most important advance in immunology in the past hundred years. Previous models of antibody formation were developed in the absence of essential information concerning the chemical nature of antibodies, the cell types responsible for antibody production, and how the immune system “knew” what specificities needed to be synthesized. In 1900, Paul Ehrlich proposed the side-chain theory of antibody formation. This was criticized due to a lack of knowledge of antibody structure. Until the 1950s, the most logical explanation of antibody formation was that the antigen served as a template to instruct cells to produce complementary binding molecules. However, information about the role of the amino acid sequence of proteins in determining molecular structure and the mechanisms of protein synthesis made instruction models difficult to defend. During the 1950s, several selection models were proposed. Niels Jerne proposed the natural selection hypothesis that moved the field from antigen instruction to antigen selection. Finally, F. Macfarlane Burnet offered a model, the clonal selection theory, that proposed the existence of a large number of antibody-forming cells, each of which is genetically preprogrammed to produce a unique antibody specificity. A similar model was simultaneously proposed by David Talmage. This theory has withstood numerous attempts to disprove it and is now the basis for our current understanding of the immune system.