The Extended Clonal Selection Theory

“Table 1. Nine propositions.

Al. The stereospecific segment of each antibody globulin is determined by a unique sequence of amino acids.

A2. The cell making a given antibody has a correspondingly unique sequence of nucleotides in a segment of its chromosomal DNA: its “gene for globulin synthesis.”

A3. The genic diversity of the precursors of antibody-forming cells arises from a high rate of spontaneous mutation during their lifelong proliferation.

A4. This hypermutability consists of the random assembly of the DNA of globulin gene during certain stages of cellular proliferation.

A5. Each cell, as it begins to mature, spontaneously produces small amounts of the antibody corresponding to its own genotype.

A6. The immature antibody-forming cell is hypersensitive to an antigen-antibody combination: it will be suppressed if it encounters the homologous antigen at this time.

A7. The mature antibody-forming cell is reactive to an antigen-antibody combination: it will be stimulated if it first encounters the homologous antigen at this time. The stimulation comprises the acceleration of protein synthesis and the cytological maturation which mark a “plasma cell”.

A8. Mature cells proliferate extensively under antigenic stimulation but are genetically stable and therefore generate large clones genotypically preadapted to produce the homologous antibody.

A9. These clones tend to persist after the disappearance of the antigen, retaining their capacity to react promptly to its later reintroduction.”

Lederberg, J. Science 129:1649-1653, 1959

Nobel Prize 1958