REGULATION 161 



life; it has acquired an 'enduring immune tolerance' towards this foreign 

 substance (Billingham et ah, 1953). An unresponsive period in which an 

 aduh behaves in this respect as a newly-born animal can be observed after 

 irradiation with a high dose of X-rays (Dixon and Maurer, 1955). Injection 

 of a very large amount of antigen can have similar effects (for a review see 

 Chase, 1959). The recognition of self and non-self, and the adoption as 

 'self of an antigen injected during an unresponsive period raise the most 

 challenging problems of the control of antibody synthesis. Cytological 

 observation with fluorescent antigens shows that after the first antigen 

 injection, thousands of cells in the lymph nodes may pick up the antigen; 

 but antibody appears in a much smaller number of these cells, and after a 

 few days antibody is demonstrable only in a few cells. In a secondary 

 response, many hundreds of cells containing traces of antibody can be seen ; 

 they are scattered throughout the areas where the antigen was deposited 

 after the first injection. These cells seem to spring up independently and to 

 multiply, so that their descendants often coalesce to form clumps of cells 

 (Coons, 1958). 



Immunological response is thus associated with processes of cell 

 multiplication and difterentiation. 



If two antigens A and B are injected into the same animal, and the antibody 

 producing cells are located by the Coons' method using a diff"erent 

 fluorescent marker for each antigen, it is observed that antibodies reacting 

 with each individual antigen are often produced by difl'erent plasma cells, 

 as if certain cells had specialized in the production of antibodies against 

 antigen A, and others against antigen B (White, 1958). The same fact was 

 observed by a completely diff"erent method. Tissues from an immunized 

 animal can continue to produce antibodies in vitro (Fagraeus, 1948). Cells 

 of lymph nodes of a rabbit immunized against two different bacteria were 

 isolated in microdrops, and tested for the production of antibodies against 

 each bacterium species. About 10 per cent of the isolated cells produced 

 one or the other antibody, but none were found to produce both (Nossal 

 and Lederberg, 1958). However, in similar experiments with rabbits im- 

 munized against phages T2 and T5, 8 per cent of the isolated cells produced 

 antibody against one or the other phage exclusively, but about 2 per cent 

 produced both types of antibodies (Attardi et al., 1959). These results 

 indicate that when an animal is injected with two different antigens, in- 

 dividual cells often form one species of antibody only, but formation of 

 one antibody does not prevent the cell from making another antibody at 

 the same time. 



Burnet (1959) has proposed a new theory which takes in consideration 

 the enduring immune tolerance, the fact that antibodies are not produced 

 by all individual cells of the competent organs, and that antibody producing 

 cells do multiply. Burnet assumes that the mesenchymal tissues are made 



