HOMOGRAFT IMMUNITY 



When mice are given a certainly lethal dose of 900-1000 r 

 whole body X-radiation, they can be saved by injection of 

 bone-marrow cells from a normal mouse. Bone marrow 

 from mice of the isologous strain is most effective but cells 

 from other strains are often satisfactory. In such cases the 

 mouse (Ford et al. 1956) can be shown to have adopted the 

 foreign cells permanently and to have developed tolerance 

 to a graft of the donor skin (Main and Prahn, 1955). Graft 

 intolerance of the host is very frequently shown in these 

 experiments. When the donor has been immunized and is 

 producing antibody, the new host will show the appear- 

 ance of and increase of this antibody (Mitchison, cited by 

 Ford et al. 1956). Rat bone marrow may be used to save 

 mice and in satisfactory experiments it can be shown that 

 rat gamma globulin is being produced (van Bekkum and 

 Vos, 1957). 



In most instances the rat cells in such mice are eventually 

 replaced by mouse cells. 



It will be obvious that while this is happening some form 

 of tolerance must have been developed by the graft cells 

 producing rat antibody for the mouse albumin still circulating 

 and other accessible mouse determinants. This is part of the 

 problem discussed in the next section. 



On the clonal selection theory one assumes that in lethally 

 irradiated animals there is an elimination of the vast majority 

 of representatives of all antibody-producing clones and the 

 foreign cells have an opportunity to become implanted and 

 apparently overwhelm the few host survivors that can react 

 with the foreign determinants that have been introduced. 

 It is of much interest that when the irradiated mouse has 

 been previously immunized with tissue of the donor strain, 

 then the foreign bone marrow cannot save the irradiated 

 mouse. This, on the clonal selection theory, would mean that 

 the immunized mouse has a large population of cells 

 of the appropriate clones, many of them perhaps in the 

 less radio-sensitive form that seems to be associated with 



89 



