IMMUNOLOGICAL TOLERANCE 



(iii) It is likely to settle in the cortical regions of lymph 

 nodes and initiate a clone of cells which are immuno- 

 logically more reactive. 

 (iv) With considerably greater uncertainty it can be 

 suggested that this activated cell undergoes a partial 

 labilization of the section of the genome concerned, and 

 acquires a probably correlated capacity to accept 

 information by transduction from other activated cells 

 in the vicinity. 

 Second contact with Z will, depending principally on its time- 

 relation to the first, produce either destructive or prolifera- 

 tive responses. Under the appropriate conditions the stimulus 

 will result in active protein synthesis and liberation of 

 antibody. 



On this basis it can be suggested that exposure of normal 

 mesenchymal cells to what is equivalent to endotoxin plus 

 specific antigenic determinants, as in Harris and Harris' 

 experiments, will have the following effects. Most cells will 

 be activated and those which for any reason carry sites 

 corresponding to the foreign antigenic determinants will be 

 stimulated to take on a secondary type of antibody-producing 

 activity with rapid proliferation when they reach an appro- 

 priate site; for example, local lymph nodes and spleen. The 

 possibility is also not excluded that injection of cells and 

 antigen in the irradiated host may reactivate antibody- 

 producing mechanisms which have been inhibited by the 

 irradiation, so that some of the early antibody production 

 may be due to the recipient's cells. 



More detailed study, including if possible search in lymph 

 nodes and spleen for antibody-producing cells, and an esti- 

 mate of the number of cells required to produce the observed 

 amount of early antibody is clearly needed. It could con- 

 ceivably show that the number of cells and the time available 

 for their proliferation are inadequate to account for the 

 results on the clonal selection theory in its original form. 

 Only under such conditions would it be necessary to adopt 



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