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DISCUSSION 



Dr. Nossal: As regards this extraordinarily important question of whether 

 'secondary disease' is due to reaction of the graft against the host, or of the host 

 against graft — we have been performing what I think are extremely simple experi- 

 ments which may have some bearing on this question, and I should like your views 

 on it. The design follows those of Lorenz and Jacobson, and we use an outbred 

 randomly mated strain of rats, which are given a large sub-lethal dose of irradiation 

 of the order of 500 r delivered at a rapid dose rate. In the course of certain immuno- 

 logical experiments we have transplanted tiny fragments of spleen to the peritoneal 

 cavities of these rats. Now we find that, as early as three days after such homografts, 

 a large proportion of the cells of the graft take on basophilic staining, eccentricity of 

 the nucleus and all the characteristics that Fagreus has described for the immature 

 plasma cells. After some three or four more days these cells, which now form the 

 majority of the live cells left in the graft, are typical marschalk-type plasma cells. 

 Similarly, when a single-cell suspension of such spleen cells is injected into the 

 peritoneal cavity, a very similar sequence of events is obtained in the draining 

 mesenteric lymph-nodes, and to a lesser extent in the lymph-nodes in distant parts 

 of the body. I was wondering. Sir, whether you have observed this phenomenon 

 with spleen cells, and whether you would agree that it is at least consistent with the 

 view that the grafted cells are making antibodies to the host. 



Dr. Loutit: This seems to me to be a very admirable approach, and I tliink that the 

 conditions are not quite the same, but perhaps you will correct me. 500 r to the 

 outbred rat, I would guess, is not the LDg^, but pcrhajjs an LDr, or LD],,. so that in 

 the first place you have not, presumably, completely eliminated the host's capacity 

 to regenerate its own tissue, but you have shown that the grafted tissues do grow 

 initially at any rate and do produce this deviation towards plasma cell-type. Our 

 experience is that if we take the LD,,,,, mouse and give it restorative treatment, not 

 bone marrow but bone marrow plus spleen, adult spleen, or bone marrow plus 



54 



