380 DISCUSSION 



Billingham: Dr. Silvers and I have done this with the CBA to A mouse 

 strain combination where splenic cells at the 7 million cell dosage level 

 only cause about 45 per cent mortaUty through runt disease, whereas i 

 million axillary or brachial node cells cause about 70 per cent mortality, 

 and almost 100 per cent of the recipients of 2 milHon node cells succumb. 

 We wondered why increasingly high dosages of spleen cells failed to 

 increase the incidence of runt disease above 50 per cent in view of the 

 number of immunologically competent cells that must be present. 

 We therefore tried to simulate a spleen cell suspension by mixing a 

 potentially lethal dosage of 2 million node cells with about 10 million 

 bone marrow cells. The presence of the latter significantly lowered the 

 mortality that would have been caused by the node cells alone, through 

 a sort of "buffering" action. When attempting to transfer runt disease, 

 one is inevitably transferring "activated" immunologically competent 

 cells with a considerable number of non-immunologically competent 

 cells that may be of donor or host origin. These may exert a similar 

 sort of buffering effect, so that overt runt disease fails to appear. This 

 postulated buffering action may be the outcome of a competition for 

 sites in their new host on the part of cells of different lineages. 



Voisin: Cytologists tell us that the spleen in the rodents is cytologic- 

 ally like a mixture of bone marrow and lymph nodes and this might 

 explain some of your results. 



Michie: About the buffering effect — you were also varying the total 

 cell dosage, weren't you, so that it might have been an overflow effect, 

 dependent on your total cell dose ? 



Billingham: That is possible. 



Brent: But what happens to the cells when they "overflow" — where 

 do they go ? 



Medawar, Brown and I have attempted to eliminate the donor's cells 

 from tolerant adult mice — mice which had been made tolerant by neo- 

 natal injection. In adult mice the transfer of large volumes of hyper- 

 immune serum doesn't appear to have any adverse effect on the per- 

 sistence of the donor's cells. There seems to be a real difference here 

 which may depend on either the age of the animal or the age of the 

 donor cell, presumably the age of the animal. When you continue 

 your attempts to remove donor cells in older mice it will be very 

 interesting to see when you get a fadeout, if you get a fadeout at all. 



