REGULATION 157 



bodies, these become strongly labelled (Green and Anker, 1954; Askonas 

 et ah, 1956; Taliaferro, 1957). Production of antibodies therefore rests on 

 the synthesis of new specific proteins all the way from amino acids. 



The use of a protein antigen coupled with a fluorescent dye makes it 

 possible to locate on tissue sections the cells which contain the corre- 

 sponding antibodies: the fluorescent antigen is bound or precipitated in 

 situ by the antibodies (Coons and Kaplan, 1950; Coons, 1958). It was shown 

 by this method, completed by tracer experiments (Askonas and White, 

 1956) that antibodies are produced by individual cells or by groups of cells 

 of the reticuloendothelial system, the plasma cells, which are found 

 especially in the lymph nodes and in the spleen. 



Antibody production thus reflects the de novo synthesis of specific 

 y-globulins by specialized cells under the stimulus of an antigen. Super- 

 ficially at least, this phenomenon is comparable to the induced synthesis of 

 enzymes. The antigen, like the substrate of an enzyme, induces the 

 synthesis of a protein which combines specifically with it. 



Obviously antibody formation raises the same problems as induced 

 enzyme synthesis. The most fundamental question, in the present perspec- 

 tive of protein synthesis, is whether the antigen brings to the antibody 

 producing cell part of the structural information relative to the antibody, 

 or whether the antigen simply triggers a ready-made machine to produce a 

 protein the structure of which is completely specified by a gene. 



The first theory of antibody production (Ehrlich, 1900) assumed that the 

 antigen, through chance affinity, binds certain receptors or special out- 

 growths of a cell surface ; the cell reacts by replacing the bound receptors 

 by two or more new ones, part of which are cast oflF in the blood as anti- 

 bodies. According to this view, the antibody structures pre-exist, the 

 antigen simply stimulates their production and their release into circula- 

 tion; it selects an antibody out of many, but it does not bring any structural 

 information to the antibody producing system. 



Landsteiner (1933) coupled proteins with various azaaryl groups under 

 conditions which do not cause denaturation. He showed that such sub- 

 stituted proteins are good antigens, and that the antibodies that they 

 evoke in the rabbit are quite specific of the artificial chemical groups 

 bound to the protein. Using substituents in which tartaric acid residues 

 had been introduced, he showed that the antibodies can even distinguish 

 between L and D isomers. These fundamental studies established that 

 antibodies are specific of individual chemical groups in the antigen mole- 

 cule, rather than of the molecule as a whole. It was clear also that anti- 

 bodies can be evoked by many kinds of chemical structures, including 

 some which are not likely to ever come in contact with a rabbit, were it not 

 for the deliberate intervention of an organic chemist. It seemed incredible 

 that the animal could possess a ready-made specific antibody to cope with 



