IMMUNOLOGICAL TOLERANCE 



a majority of the mice develop tolerance to skin grafts from 

 CBA. On the other hand, if C57 mice are used as donors to 

 new-born A mice, an intravenous inoculation of spleen cells 

 is virtually always productive of 'runt disease' and very 

 often the mouse dies rapidly. In order to produce the effect 

 mature lymphoid tissue must be used. A point of very great 

 interest is that thymus cells are fully competent to produce it; 

 in other words thymocytes are functionally as well as mor- 

 phologically equivalent to lymphocytes. 



The indications are strong that the antigens concerned in 

 homograft immunity (that is, those concerned in provoking 

 accelerated rejection of a graft in an immunized animal) are 

 the same as those involved in tolerance phenomena. This 

 makes the recent finding of Billingham et al. (1956^) that the 

 antigen involved in homograft immunity appears to be a 

 DNA-nucleoprotein, of special interest. If to a white mouse 

 of strain A, rendered tolerant to, and carrying a skin graft of, 

 strain B (black), a second graft of lymph node from a normal 

 strain A mouse is made, an immune response against B cells 

 develops and the graft is destroyed. This suggests strongly 

 that, presumably at each mitosis, potentially antigenic 

 nucleoprotein molecules are liberated into body fluids, that an 

 important part of the development of tolerance to body con- 

 stituents is directed toward these and that the nucleoprotein 

 antigens are capable of producing only cell-borne antibody. 

 There is an insistent suggestion here that the liberated DNA 

 nucleoprotein molecules may play an important role in the 

 mutual control of cellular growth, and that special mesen- 

 chymal ceil clones may be differentiated during development 

 to deal with any anomalous liberation of such material. 



Since all modern theories of antibody production are 

 designed to allow an interpretation of tolerance, it is un- 

 necessary to elaborate how the clonal selection theory 

 functions in this respect. It is more important to consider the 

 production of X-ray chimaera and the various phenomena 

 of partial tolerance. 



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