CLONAL SELECTION THEORY 



a body component or any foreign determinant artificially 

 introduced results in the elimination of cells carrying such 

 sites, and if all such clones are eliminated full tolerance is 

 established. 



The next phase is the gradual change in the response to 

 contact with antigenic determinant. From the lethal effect 

 seen in the early stage it changes, perhaps with an inter- 

 mediate phase of damage and partial recovery, to stimulation 

 of protein synthesis and, in the appropriate tissue environ- 

 ments, active proliferation to produce plasmacytoid cells and 

 lymphocytes with active antibody-liberating capacity. 



This sequence, shown schematically in Table 2, provides 

 the outline of what can be called the clonal modification of 

 Jerne's hypothesis or the clonal selection theory. 



6. Comparison of theories 



In comparing the four modern theories that I have outlined, 

 the first requirement is a decision over the fundamental 

 difference between the direct template theory and the other 

 three. If antigenic determinants are needed to take a direct 

 part in all antibody production, then there is no scope for 

 discussion of the problem along genetic lines and no way of 

 providing an interpretation of such phenomena as the non- 

 antigenicity of self-components, immunological tolerance, 

 cell-borne antibody or modification of antibody character 

 with time and differing degrees of stimulation. As a general 

 hypothesis to cover immunological behaviour, this theory is 

 manifestly inadmissible. The only question that really arises 

 is whether, on a background of one of the other three hypo- 

 theses, a new mechanism has been superimposed by which 

 production of urgently needed protective substance may be 

 accelerated. This might take the form of an enforcement of 

 somatic mutation in the required direction in those cells 

 whose natural pattern fitted best for this function. This would 

 be a rather unhappy hybrid. 



For reasons that have already been given, we believe that 



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