176 MICHAEL FELDMAN AND DAVID YAFFE 



compatible with the induction of immunogenetic changes, seem 

 to have no direct correlation with the immunogenetic conditions 

 within the chimeras. Furthermore, the fmal result with tumour 

 lines susceptible to the homograft reaction, but themselves not 

 immunogenic, can hardly be reconciled with a selective pressure 

 involving an immune mechanism. An immunological pressure 

 could have selected out either cells which can resist the homograft 

 reaction, or which have lost the histocompatibility antigens, the 

 target for the homograft reaction. SBLx cells, being susceptible 

 to the homograft reaction, could have no selective advantage. It 

 seems relevant to point out that, unhke our experiments on the 

 immunizing effect against SBLx of a simultaneous graft of SBLi, 

 the experiments of Klein and Klein (1954) on the transplantation 

 of a mixed population of his F^-adapted tumour cells and the 

 original strain-specific tumour cells resulted in the selection of the 

 adapted tumour, which gave 66 per cent of lethal takes in Fg 

 animals. However, although a process of immunoselection does 

 not seem to play a decisive role in the mechanism of adaptation 

 of SBLx, other processes of selection cannot be ruled out. To 

 differentiate between a selective mechanism and a mechanism of 

 induction of direct genetic change within the tumour cells, we 

 are trying now (i) to test the incidence of change when lower 

 cell doses are transplanted in radiation chimeras, and to apply the 

 fluctuation test to results of adaptation experiments, and (2) to 

 establish clones of the strain-specific tumours, and test the inci- 

 dence of acquired homotransplantability in individual clones. 



The properties acquired by the homotransplantable tumours, 

 namely their decreased immunogenicity, associated with a high 

 susceptibility to the homograft reaction, require further analysis. 

 The apparent suppression of antigen production could derive 

 either from a quantitative change, or from a qualitative change, 

 of the original H-2 genetic complex. A quantitative change, such 

 as a repression or switching-off in gene action of the H-2 complex, 

 might have caused a low production of antigen, below the 



