202 MORTEN SIMONSEN 



should expect a specifically preimmunized donor to produce a 

 higher number of foci on the membrane than would a non- 

 preimmunized donor (an experiment, which, to my knowledge, 

 has not yet been carried out). Likewise, in the spleen assay system, 

 fewer immune cells than normal cells would be expected to pro- 

 duce the same degree of spleen enlargement (i.e. a high Factor of 

 Immunization). 



As the results have clearly shown, this expectation is fulfilled 

 very well for immunization of C3H with AKR antigen, less well 

 with A antigen, rather poorly with ST/ A antigen, and hardly at 

 all with DBA/ 2 antigen. It is of course the data of Table II for 

 hyperimmunized donors which are most relevant here, as these 

 are the ones where the stimulated clones have had the best 

 opportunity for expansion. 



If we assume, as Burnet and Burnet also did in the above 

 quotation, that active immunization also leads to a higher reac- 

 tivity per cell, there seems virtually no space left for clonal 

 selection in the combination with DBA/ 2. 



It seems to me, however, that the results can still be very well 

 accommodated into a clonal selection frame of thought if the 

 hypothesis is formulated as follows. 



(a) All immunologically competent cells in the same individual 

 are originally endowed with low-grade reactivity (affmity) to all 

 antigens (essentially Lederberg's idea of clonal selection on an 

 intracellular basis, 1959). 



(b) In the process of ontogeny, affinities to self-components are 

 eliminated or suppressed through a process of overloading with 

 antigen (Burnet, 1959). 



(c) Throughout the life of the individual, mutational losses 

 occur on the various genetic loci which are determining the inborn 

 immunological affinities of the cells. This leads to differentiation 

 in cellular clones, some of which have lost some affinities, whilst 

 others have lost other affinities. 



(d) The rate at which loss-mutations occur is very different for 



