MECHANISM OF ANTIBODY FORMATION 51 



the antigen-antibody complex and purified by pbysico-chemical means, 

 has been shown to possess the serological species-specificity of normal 

 globulin and the acquired additional property of reacting specifically 

 with the homologous antigen. It would be of interest, therefore, to 

 consider the metabolism of normal and immune globulins, and other 

 proteins as well. Experimenting with young and adult rabbits, Cannon 

 (1945), Cannon, et at (1943), and Wissler, et al (1946) reported 



the long accepted indistinguishable specificity of the ■proteins of the ocular lens, 

 demonstrated the species specificity of the proteins of lens from chicken and fish, 

 though this characteristic was not so evident in the closely related species swine and 

 sheep. 



According to Lewis (1934) casein is iso-antigenic. Sera of two goats, one immunized 

 with goat casein, and the other with cow casein, reacted equally well with both 

 caseins. The chief objection to these results seems to be the method of the prepara- 

 tion of casein which involved precipitation with normal acids and mechanical 

 stirring at the rate of 2000 to 3000 revolutions per minute. The system was exposed 

 to O.IN acid (final concentration) for six to eight hours. The precipitated casein 

 was washed five times vidth water, twice with 95 per cent alcohol and three times 

 with ether. It was then dried by spreading. Under these conditions the species 

 specificity of native casein might easily be destroyed as a result of denaturation, and 

 behave like a non-specific antigen. For it has been showoi that, in contrast to native 

 rabbit serum protein, denatured rabbit serum would produce antibody in the rabbit 

 (Landsteiner, 1945). 



One may also call to attention the possible non-specific antigenicity of the pros- 

 thetic group, serine-phosphate or glutamyl-serine phosphate (Levene and HUl, 1933; 

 Schmidt, 1933, 1934), common to all mammalian caseins. The phosphate in casein 

 is ortho-phosphoric acid esterified with the hydroxyl group of serine. It is a relatively 

 strong acid and its titration curve shows a sharp inflection between pH 6.0 and 7.5, 

 due to, possibly, secondary ionization of the phosphoric acid group. The antigenicity 

 of phenyl phosphoric acid is an established serological fact. 



Another possibility which may be worth mentioning is the fact that casein is a pro- 

 tein synthesized by the female mammal by an organ which is entirely inactive and 

 undeveloped in the male. For these reasons one may be tempted to consider it as a 

 protein foreign to any mammalian system. Bruynoghe (1935) reported that the egg- 

 white from a hen, precipitated with ammonium sulfate and dialyzed to remove the 

 salt, produced specific antibody in the same hen and in a rooster. He assumed that 

 egg-albumin is a protein totally different from the components of serum and has not 

 participated at all in the cellular metabolism of the animal. In this manner, he con- 

 cluded, egg-albumin might exercise iso-antigenic activity. However, one must keep 

 in mind the fact that egg-albumin is very susceptible to denaturation during its 

 preparation. 



Ferritin is a metal protein of 500,000 molecular weight and contains from 17 

 per cent to 23 per cent Fe. Granick (1943) found that apoferritin derived from 

 crystalline ferritin, with the exception of a slight reaction between horse apoferritin 

 antibody and dog apoferritin, is immunologically species specific, and non-organ 

 specific. Protein crystals of ferritin obtained from one organ reacted with antiserum 

 to ferritin crystals obtained from another organ. 



Bonnichsen (1947) found that liver and blood crystalline catalases were serologi- 

 cally identical; the values for nitrogen distribution, histidine, arginine, lysine, tyro- 

 sine, cystine, glutamic and aspartic acids were found to agree writhin the limits of 

 error for both catalases. 



