DISCUSSION 



Medawar: Could I propose what seems, superficially perhaps, to be 

 an alternative interpretation of the difference between the strong and 

 the weak antigen ? — that the relatively weak antigen is an antigen in 

 respect of which the abihty of a host cell to respond matures relatively 

 late in life ? This is making the distinction between strong and weak 

 antigen turn upon chronological rather than purely numerical matters. 

 This interpretation would explain the empirical fact that the weaker 

 an antigen, in the transplantation system, the later in life is it possible 

 to induce tolerance. You needn't assume that the population of res- 

 ponding cells is heterogeneous; all you have to assume is that com- 

 petence to respond to different antigens matures at different times. 



Simonsen: If you take the induction of tolerance in adults by the 

 parabiosis technique in which you parabiose with F^ hybrid, I suppose 

 on your assumption it should have had time enough to develop re- 

 activity towards even the weakest antigens, since these are fully adult 

 mice. But the difference between the strong and the weak antigens still 

 remains ; it is much easier to induce tolerance towards the weak antigens 

 than to the strong. 



Medawar: That is what I would expect in the adult. According to 

 McKhann's recent results on co-isogenic strains differing at H-3 — 

 whether you get immunity or tolerance varies with the dosage of 

 spleen cells: a low dose of cells will excite immunity but a higher dose 

 very easily excites what one could well describe as tolerance, though I 

 don't think the analysis has gone far enough to show whether it is 

 tolerance or not. One ought not to forget that there is a special sense 

 in which antibody-forming cells might form a heterogeneous popul- 

 ation : they may be heterogeneous in the sense that different immuno- 

 logical faculties mature in those cells at different times. Is this idea 

 eliminated by anything we know ? 



Michie: Are you suggesting that in the adult mouse there is complete 

 failure of maturation towards some weak antigens — even when the 

 mouse is "middle-aged" ? 



Medawar: No. I was wondering whether it was possible to think that 

 in an adult mouse only a relatively small proportion of the cell popul- 



