MECHANISM OF ANTIBODY FORMATION 119 



possessing Vi the size of the original antitoxin molecule, was distinct 

 from the normal serum proteins. It would thus seem that the antitoxin 

 freed from the normal serum components behaved as a new species of 

 protein molecule. This is understandable if we accept the interpretation 

 that antigens function as catalysts, similar in this respect to other 

 specific enzymes involved in protein syntheses. 



Related to the above finding, are the results of a study by Weil, 

 Parfentjev and Bowman (1938). They reported that antibody globulin 

 can be subjected to proteolytic digestion in a manner whereby it almost 

 completely loses its ability to incite the formation of specific antibodies, 

 without suffering loss in antitoxic properties. Diphtheria antitoxic 

 globulin after partial peptic digestion at pH 4 and 4.5 was from 70 to 

 80 per cent non-coagulable by heat. The antitoxic component of the 

 digest was separated by ammonium sulfate fractionation and purified 

 by dialysis. The traces of remaining pepsin were eliminated by a 

 freshly prepared suspension of calcium phosphate. This preparation 

 was compared, in various serological and animal tests, with normal and 

 immune horse plasma, and antitoxin globulin salted out with am- 

 monium sulfate. Absorption experiments demonstrated directly that 

 the antitoxic property was in the hydrolytically cleaved part of the 

 solution and not in the unchanged fraction. The results of experiments 

 showed that unimpaired— and even increased— antibody-function was 

 possessed by this derivative of the antibody molecule. This derivative 

 was so far removed that its property to function itself as an antigen was 

 eliminated, and wdth it all traces of its original connection, detectable 

 by immunological methods. The above results show that an antibody 

 molecule can be stepwise split into various derivatives. In the first 

 example, its serological relationship to normal serum proteins was 

 eliminated without a loss in antigenic and antitoxic properties. In the 

 second example, its antigenic relationship was eliminated without a 

 loss of antitoxic activity. These facts show strongly that the groups 

 responsible for the properties of antitoxin to combine with and 

 neutralize toxin are distinct molecular entities derivable from the larger 

 whole molecules. 



In a similar study, Peterman (1946) reported that the early effect of 

 papain or bromelin on horse diphtheria antitoxin and beef serum 

 globulin is quite similar to that of pepsin and trypsin. The molecules 

 are split into halves. On prolonged digestion, these halves are split into 



