TOLERANCE TO ANTIGENS 



and Weigle, 1955) will itself result in a great decrease in 

 antigenic stimulus so that probably very little antibody is 

 actually being liberated. The essence of the matter is that the 

 antigen takes the form of a tightly bound insoluble and 

 enzymatically insensitive complex. 



3. Natural antibodies 



In the clonal selection hypothesis, natural antibodies are not 

 of such primary importance as they were in Jerne's theory. 

 There is no requirement that all the clones should be 

 represented by corresponding globulin molecules in the 

 plasma, although this possibility is equally not excluded. In 

 fact, it is highly characteristic of most ' natural antibodies ' 

 that they do not appear until some days or weeks after birth. 

 If there is a process of ' clone elimination ' during embryonic 

 life to prevent the maturation of clones adapted to react with 

 body determinants, plasma globulin can play no part in it. 



Of the natural antibodies produced in man, the anti-^ 

 and zxiti'B uoagglutinins are the best known and the T ag- 

 glutinin active against RDE-treated red cells is another which 

 has been studied in my laboratory. Reasons have been given 

 already for the assumption that cells capable of producing 

 the woagglutinins are genetically produced and that iso- 

 agglutinins reactive with whatever antigen is present in the 

 body are not developed because of specific elimination of the 

 clones of cells which would eventually produce the iso- 

 agglutinins in question. There is no indication as to the site 

 or histological nature of the cells responsible for their produc- 

 tion in adult life, but the fact that they are absent in con- 

 genital agammaglobulinaemia speaks strongly for their 

 production, like classical antibodies, from certain clones of 

 plasma cells. It is evident that similar types of modification 

 with development must be ascribed to these cells as to those 

 concerned with antibody production proper. 



At an early stage in the development of a child of blood 

 group A, we must postulate cells potentially, but not actually, 



95 



