IMMUNOCHEMISTRY 



For the first time, complement "belonged" and this Flying Dutchman 

 of immunology was at rest. 



Stepping out with these quantitative methods, immunochemistry 

 has also contributed to the interpretation of isotope studies in protein 

 metabolism. Compounds of heavy nitrogen were found by Schoen- 

 heimer and his group to slip in and out of body proteins and their 

 constituent amino acids with unexpected speed and thoroughness. 

 In collaboration with these biochemists it was found possible to work 

 not only with labeled nitrogen but with labeled protein — antibody — 

 as well. In a rabbit immunized with type III pneumococci, anti- 

 body, quantitatively separable from the other serum globulins, was 

 found to take up dietary nitrogen at about the same rate as these 

 other proteins (21,34). All of this seemed eminently proper until 

 another test was made adopting TrefTers' idea of injecting a similarly 

 immunized rabbit with a difTerent antibody, type I pneumococcus 

 anticarbohydrate, from another rabbit. The type Ill-immunized 

 rabbit was fed heavy nitrogen. Here, then, were labeled dietary 

 nitrogen and two labeled indicator proteins, one being produced 

 (and destroyed) by the animal, the other merely being metabolized. 

 Each indicator protein in the rabbit's serum, drawn at intervals, was 

 quantitatively and independently precipitable by the corresponding 

 specific polysaccharide and so separable from the other serum proteins. 

 What happened was that, while the type III antibody quickly took 

 up heavy nitrogen as before, the passively injected type I antibody, 

 which was merely circulating in, but was not being elaborated by, 

 the test rabbit, remained free from heavy nitrogen. This was taken 

 to indicate that heavy nitrogen fails to enter serum protein molecules 

 which were complete at the start of heavy nitrogen feeding, but be- 

 comes part of the structure only of those proteins which are being 

 constantly synthesized. As a by-product, quantitative studies of the 

 rate of disappearance of heavy nitrogen from antibody indicated a 

 half-life (with respect to synthesis vs. destruction) of about two weeks, 

 much the same as that of other serum proteins in this animal. 



Incidentally — and this was overlooked at the time — the absence 

 of N^^ in the passively injected type I antibody, after precipitation with 

 its homologous type-specific polysaccharide and washing under standard 

 conditions, affords as rigorous a test as has ever been made of the speci- 

 ficity of immune precipitation and the validity of the assumption under- 



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