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IMMUNOLOGICAL STUDIES ON LETHALLY 

 AND SUB-LETHALLY IRRADIATED ANIMALS* 



G. J. V. NossAL and Lois Larkin 



]Valtrr and Eliza Hall Institute, Royal Melbourne Hospital, 



Melbourne Victoria 



Whole-body irradiation profoundly depresses the immune response^. 

 This phenomenon has been recognized by many \\orkers as a useful tool in 

 the investigation of problems connected with the cellular aspects of immunity. 

 After large doses of whole-body irradiation, an animal is immunologically 

 neutral for some time, and can act as a host for immunologically competent 

 cells. The behaviour of these transferred cells can then be studied in a 

 variety of circumstances, and it is this type of experiment which will be 

 reported in the present paper. 



In recent years there has been great interest in the cellular aspects of 

 immunity inspired by experimental findings in several fields. First there is 

 the work, of which Dr. Loutit is one of the pioneers, on the saving of lethally 

 irradiated animals with isologous, homologous and heterologous bone mar- 

 row. The resulting chimaeras and the immunological reactions taking place 

 during the recovery phase have been the subject of intensive study in many 

 laboratories. Then there is a finding by Simonsen^ which has most interest- 

 ing implications. He finds that when adult fowl leukocytes are injected into 

 chick embryos, they lodge in the embryo spleen, proliferate extensively, and 

 appear to make antibodies to the antigens of the host embryo, resulting in 

 erythroblastosis foetalis, with the appearance of Coombs-type antibodies, 

 and eventual death of the embryos owing to haemolytic anaemia. More- 

 over, when these cells, now proliferating in the host spleen, are transferred to 

 further embryos, the same pattern is repeated, and this type of passage can 

 be carried on indefinitely. This suggests that antibody-producing cells 

 can replicate functionally for an indefinite period in a series of embryonic 

 host spleens. 



Stimulated by these and other findings. Sir Macfarlane Burnet^ has 

 postulated an entirely new concept of antibody formation, called the clonal 

 selection theory. This theory has provided the background to much of the 

 work to be reported, and therefore will be discussed in some detail. 



In its simplest form, the hypothesis states that the information necessary 

 for the production of any conceivable antibody globulin resides in a normal 

 unstimulated adult animal. This information exists in the form of clones of 

 mesenchymal cells, each of which is designed to form one type of patterned 

 globulin or antibody. It is postulated that the ancestors of antibody-forming 

 cells, during embryonic development, randomize and stabilize into definite 

 clones of cells. As soon as stabilization is achieved, each cell can form one, 



* This work was supported by a grant from the National Health and Medical Research 

 Council, Canberra. 



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