STUDIES ON THE LOCUS OF ANTIBODY FORMATION. 



FREDERICK P. GAY and G. Y. RUSK, from the Hearst Laboratory of Pathology 

 and Bacteriology, University of California. 



Since the critical work of Knorr 1 on toxins it has been generally 

 accepted that antibodies are formed, not by a simple inversion of 

 antigens, but by a reaction on the part of the cells of the animal that 

 has received the antigen. Correlatively, it has been assumed that cer- 

 tain cells have a particular affinity for a given antigenic substance 

 and are presumably specifically fitted to produce the corresponding 

 antibody. Ehrlich's receptor hypothesis, while stating this assump- 

 tion more concretely, has in no instance given direct proof that any 

 particular type of cell gives rise to any given antibody. The experi- 

 ment of Wassermann and Takaki 2 that demonstrated the apparent 

 neutralization of tetanus toxin by brain substance is no longer re- 

 garded as a proof of the nerve-cell origin of tetanus antitoxin. In- 

 deed the work of Loewi and Meyer 3 - would show that injection of 

 the toxin into nervous tissue produces an increased susceptibility of 

 the animal to tetanus toxin rather than an increased resistance. 

 The fact that tetanus toxin disappears rapidly from the circulating 

 blood of susceptible animals and may soon be demonstrated in the 

 central nervous system would not, it would seem, prove conclusively 

 that the toxin may not also have been fixed and neutralized by other 

 body cells. At least it would seem necessary to assume that the 

 cells responsible for the antitoxin formation must first fix the an- 

 tigen. This proof of antigen fixation, indeed, constitutes one of the 

 methods that have been employed in searching for the locus of an- 

 tibody formation. The only other apparent method of determining 

 antibody origin would seem to lie in the early demonstration of 

 antibodies in given cell groups before they are demonstrable in the 

 circulating blood. 



Very little information, therefore, on the site of antibody forma- 

 tion has been gained from studies on toxin and antitoxin. Our 

 information, inconclusive as it is, has been obtained from the work 

 with other antibodies, and we would do well to consider first what 

 data have been accumulated in respect to each of the antibody 



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