IMPLICATIONS OF CLONAL SELECTION 



The second postulate, that active sites on cell surface or 

 globulin molecule can be modified to a wider reactivity by 

 somatic mutation, provides the chief agent to allow change 

 in antibody character as immunization proceeds. If the 

 primary postulates of the clonal selection theory are accepted, 

 such a result of somatic mutation is as much in order as 

 any other. 



3. The action of adjuvants 



There is no doubt that by incorporating an antigen in a 

 variety of mildly irritating and depot-producing substances 

 more antibody can be produced, and with a number of anti- 

 gens this is the only practical way of obtaining a reasonably 

 active serum. According to the classic Haurowitz and Mudd 

 theory of antibody production, the general explanation of 

 this phenomenon was that it was a complex action in which 

 the most important factor was probably the prolonged main- 

 tenance of a depot of antigen. The local accumulation of 

 a variety of mesenchymal cells could also be expected to 

 facilitate the intracellular processes concerned. 



On the clonal selection hypothesis, the first assumption 

 will be that 'sites' corresponding to the determinants of 

 antigens requiring adjuvants are present in very few clones. 

 In line with what has already been said in discussing 

 secondary responses, it is highly probable that minor degrees 

 of somatic mutation are constantly occurring, so that we can 

 retain the possibility that mutation and selective prolifera- 

 tion may eventually build up, from parental cells with only 

 minor reactivity, clones which react well with certain deter- 

 minants. For such a process to occur the main requirement 

 is simply time and opportunity. If we have a clone with 

 a reactive site not quite appropriate to determinant Z), but 

 sufficiently close for contact to provoke activation and pro- 

 liferation occasionally, cells of this clone will multiply more 

 rapidly on the average than other clones. Mutation within 

 the clone will be more likely to occur and any favourable 



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