212 DISCUSSION 



three quite well established facts of serology are a sort of translation of 

 the data you presented here, aren't they ? 



Simonsen: On current hypotheses, I don't see any obvious reason why 

 the amount of prohferation in the antibody-forming machinery should 

 be different, between strong and weak. 



Mitchison: You may be working up to a ceiling. A rabbit can only 

 make, say lo mg. of antibody per ml. You may do well to begin with 

 but there is less room for expansion subsequently. 



Simonsen: I fmd it hard to beheve that it is all due to increased re- 

 activity of cells which do not multiply. I think it is well established, 

 particularly in classical immunology, that hyperimmunization is 

 accompanied by proliferation of antibody-forming cells. 



I will gladly accept the analogy you draw to classical antigens which 

 elicit their maximum response with different rapidity, some quickly and 

 others slowly. But this fact is itself in need of an explanation. Who 

 knows, perhaps this has also to do with heterogeneity in the population 

 of immunologically competent cells, similar to the one I have postulated. 

 Also the antigens you are mentioning inight be classifiable in terms of 

 how big a fraction of the cell population they have affmity to, when 

 they are first injected. Perhaps there are also obhgatory antigens among 

 the classical ones, whilst others are more or less facultative. 



Michie: Another possibihty which would also fit in with the facts is 

 that with strong histocompatibihty antigens in the mouse, you have 

 already got pre-formed immunity; this could also give the same 

 correlation that you've shown us, couldn't it ? 



Simonsen: I think that pre-formed immunity, as far as circulating 

 antibodies can be taken as a reflection of it, is ruled out. Dr. Amos 

 would know that better than I. Have any pre-formed haemagglutinins 

 in the H-2 system ever been demonstrated ? 



Amos: No. I think there seems to be some sort of non-specific 

 immunity, especially perhaps in the F^, but I don't think there has ever 

 been any convincing demonstration of haemagglutinating antibody. 



Michie: Has anybody induced splenomegaly with haemagglutinating 

 antibodies pre-formed or otherwise ? Because if not, I am not quite 

 sure if this fully meets the possibility of pre-formed immunity. 



Simonsen: I am not aware that anyone has done it. I doubt if anyone 

 has tried it seriously. I think Siskind once tried it, without success. 



