SPECIFICITY OF GENE EFFECTS 241 



in the serum — while in individuals with substance A, only anti-B is found; 

 in those with B, only anti-A is present; and in AB individuals the effects of 

 the respective genes on the antibodies are somehow neutralized? 



Before attempting to answer this question, it will be advisable to review 

 the present knowledge of the chemistry of the A and B substances of human 

 cells. See Rabat (1949). 



These antigens (blood groups, cellular characters, antigenic factors, etc.) 

 are found in nearly all the fluids and tissues of the human body. They also 

 are widely distributed throughout the animal kingdom. The A substance or 

 an A-like substance has been found, for example, in hog gastric mucosa, in 

 the fourth stomach (abomasum) of the cow, and in swine pepsin, while both 

 A and B substances have been noted in the saliva and stomachs of horses. 

 Following chemical fractionations, principally of horse saliva and hog gastric 

 mucosa, various investigators have obtained preparations with activity re- 

 lated to the A substance. These preparations have been largely polysac- 

 charide in nature. In addition to the polysaccharides, even in the purest 

 preparations, some workers have noted traces of amino acids. 



At present, while it appears that both the A and B substances of human 

 cells may be classed as nitrogenous polysaccharides, no information is avail- 

 able as to the structural differences between them. Our knowledge of such 

 specificities rests entirely upon the technics of immunology, that is, by the 

 interaction of either naturally occurring antibodies (as anti-A and anti-B), 

 or immune antibodies, with the respective substances A and B. 



The antigenic substances A and B of human cells are complex polysac- 

 charides, while the antibodies are modified globulins, or are found in serum 

 protein very closely related to the globulin fraction. If the gene which effects 

 antigen A is responsible also for the B antibody, and that for antigen B for the 

 A antibody, it would seem that here is a clear-cut case of pleiotropic effects of 

 the respective genes. This explanation runs into difficulties in AB individuals 

 which, on this proposal, should have both kinds of antibodies but actually 

 have none. In contrast, a current explanation of the reciprocal presence of the 

 antigenic substance of the cells and the antibody for the contrasting sub- 

 stances is that the antibodies for both substances (A and B) are normal con- 

 stituents of human serum. Production of the antibodies would then be con- 

 trolled by a gene or genes at another locus than that having to do with the 

 cellular substances, ij genes were involved in their production. If an indi- 

 vidual carries the gene for A, and hence has A substances widely distributed 

 throughout his body, the A antibodies are presumed to be absorbed from the 

 serum, and of course the B antibodies are left. Also, an individual with the 

 B substance would absorb the B antibodies, and the antibodies to A would 

 remain, while both anti-A and anti-B would be absorbed in an AB individual. 

 Other hypotheses are given by Wiener (1943). Unfortunately, no experimen- 

 tal test of the correctness of this or other hypotheses is likely. 



