THEORIES OF ANTIBODY PRODUCTION 



The outstanding difficulty in accepting Jerne's theory is 

 the claim that when a given type of natural antibody molecule 

 is brought to a cell by antigen, the cell then proceeds to make 

 more natural antibody molecules of the same type. The facts 

 that, in general, union with specific antigen results in partial 

 denaturation of antibody globulin, that there is no nucleic 

 acid in antibody and that homologous antibody is very 

 rapidly broken down when it is taken into a cell (Humphreys 

 and Macfarlane, 1954), all speak against the concept. 

 Talmage (1957) pointed out that it would be more satis- 

 factory if the replicating elements essential to any such theory 

 were cellular in character ab initio rather than extracellular 

 protein which can replicate only when taken into an appro- 

 priate cell. He did not elaborate this view but clearly 

 regards it as the best current basis for immunological theory. 

 Our own view is that any tenable form of Jerne's theory must 

 involve the existence of multiple clones of globulin-producing cells, 

 each responsible for one genetically determined type of anti- 

 body globulin. This immediately poses the question of how 

 the antibody-antigen complex can reach the cells, which are 

 genetically determined to produce the corresponding type 

 of antibody molecule. Clearly it would simplify matters 

 a great deal if the antigen were in a position to react with 

 natural antibody or a pattern equivalent thereto on the 

 surface of the cell which produced it. 



This is the crux of the clonal selection hypothesis. It 

 assumes that in the animal there exist clones of mesenchymal 

 cells, each carrying immunologically reactive sites corres- 

 ponding in appropriate complementary fashion to one (or 

 possibly a small number of) potential antigenic determinants. 

 This provides a population of cells which, when an appro- 

 priate stage of development has been reached, are capable 

 of producing the population of globulin molecules which 

 collectively provide the normal antibodies. When an antigen 

 is introduced it will make contact with a cell of the corres- 

 ponding clone, presumably a lymphocyte, and by so doing 



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