158 DISCUSSION 



that the faikire of splenic enlargement is therefore due to a sort of 

 internecine warfare between the CBA cells and the CBAx A cells in 

 the battleground represented by the A-line host, and is not due to an 

 effect of the original inoculum upon the A-line mouse itself 



Michie: You mean that these donor cells are thought to be tolerant 

 to A-line antigens introduced by the original inoculum ? 



Medawar: I think their reactivity may be weakened, and this might 

 account for the diminution of splenic enlargement which you 

 subsequently observed. 



Michie: This is on the basis that the A-line antigens present in the 

 day o adult inoculum are in some sense stronger or more effective ? 



Medawar: There are a lot of them — 200,000 adult cells. 



Michie: To answer this I must refer to Fig. 3 of my paper, in which 

 the dose of donor cells was varied by ten-fold dilutions. If your inter- 

 pretation were right one would expect that our phenomenon would 

 intensify as you increase the size of the original inoculum by reason of 

 a larger quantity of introduced A-line antigen. This is not what we 

 found. As we increase the quantity of initial inoculum above the point 

 which we found optimal, far from the reduction of splenic activity 

 increasing (i.e. going down on the graph), it goes back up to the base- 

 line, and, as one might expect on the simple hypothesis of the host 

 being made tolerant by the larger doses, actually overshoots. 



Medawar: It doesn't overshoot until you have injected 20 million 

 cells into a newborn mouse. 



Michie: My second comment is that the bulk of our assays have been 

 based on the alternative system that I described, where, in place of 

 living Fi hybrid cells we use a very much larger inoculum of lethally 

 irradiated CBA cells, in which case this particular point doesn't arise. 

 The basis of our interpretation in terms of an immunizing effect on the 

 newborn, is that in those circumstances where irradiated pure-strain 

 cells present the correct H-2 antigenic stimulus to the host, the pheno- 

 menon shows itself, and in those circumstances where there is either no 

 antigenic difference or there is a non-H-2 difference, we don't get the 

 phenomenon. 



Medawar: When you use the irradiated CBA cells. Dr. Michie, how 

 many do you inject into the newborn? 



Michie: A very high dosage. Our most common was 15 million 



