G. J. V. NOSSAL AND LOIS LARKIN 



cells stimulated in vitro. The neonatal animals were able to support secon- 

 darily stimulated cells only. 



These experiments have not been quite as conclusive as was hoped. We 

 have not been able to isolate a population of cells with abnormally high 

 antibody-producing potential which might represent a pure clone. However, 

 we have demonstrated that given adequate antigenic stimulation, antibody- 

 forming cells or their descendants can be serially passaged through a number 

 of hosts, with continued functional integrity. A more sophisticated approach 

 will have to be used if a clone is to be isolated. 



The final series of experiments is concerned with a rather different problem 

 related to immunological tolerance. When animals are given large doses of 

 whole-body irradiation, this is followed by necrosis of a large proportion of 

 the mesenchymal cells. Subsequendy, there is a phase of intense proliferation 



1st 2nd 3rd Ath 5th 6th 

 Passage 



Figure 5. Serial transfer of immune 

 spleen cells to adult sub-lethally irradi- 

 ated recipients: ■ — ■ immune donor; 

 • --• normal donor; X — X antigen 

 alone 



and differentiation of cells, be it the animal's own cells, or the cells of a bone- 

 marrow graft. We thought it might be possible that during this recovery 

 phase the mesenchymal cells might go through a stage of functional im- 

 maturity, corresponding to the stage represented by embryonic mesenchy- 

 mal cells. If this were the case, then the cells should be capable of being 

 made tolerant to a suitable antigen injected along with them. Dr. Loutit 

 and collaborators^ have shown that tolerance does in fact develop in lethally 

 irradiated mice to the tissues of the saving homograft in a large proportion of 

 cases. However, this problem differs little from the quesdon of whether 

 immunological tolerance to an unrelated antigen can be induced. 



Numerous workers have demonstrated that immature animals can be 

 made tolerant to foreign erythrocytes, provided that sufficiently large doses 

 are given^'^'^''. Accordingly, we lethally irradiated inbred C3H mice with 

 850 r of whole-body irradiation, and saved them with a bone-marrow 

 isograft. The next day, and thereafter twice weekly for four \veeks, the mice 

 received large doses of rat erythrocytes intraperitoneally. At the end of the 



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