THEORIES OF ANTIBODY PRODUCTION 



suggested that there were normal globuHn-producing cells 

 which ' by accident ' were potentially capable of producing 

 molecules with the configurations needed to act as iso- 

 agglutinins of the two types (and we should now add anti-i/ 

 as well) . If, however, the genetic constitution of the embryo 

 resulted in the production of A substance on red cell surface 

 or elsewhere, the potential producers of anti-^ were rendered 

 tolerant; that is, A was recognized as self and only anti-^ 

 developed. The other groups would be similarly interpreted. 

 Two haematological anomalies provide rather strong support 

 for this view. The human chimaera described by Dunsford 

 et al. (1953) was genetically with A cells from her twin 

 brother derived presumably by prenatal implantation of 

 haematopoietic cells. She showed no anti-^ woagglutinin 

 and the A cells were negative to Coombs' test. It seems that 

 the capacity to produce anti-^ which was genetically present 

 must have been inhibited or annulled during embryonic life. 

 The converse situation is to be found in persons with the rare 

 ' Bombay ' blood group anomaly (Bhende et al. 1 952) . In this 

 phenotype the cells are not agglutinated by any isoa.gg\u- 

 tinin, presumably as a result of genetic anomaly. The serum 

 contains anti-^, anti-^ and anti-//. 



This can be taken as a prototype of the kind of interpreta- 

 tion to be adopted in developing the present modification 

 of Jerne's theory. How clones to cover all possible antigenic 

 determinants can arise must be left for later discussion. We 

 assume simply that this does take place at some stage in 

 embryonic life and that mesenchymal cells, presumably 

 lymphocytes, begin to circulate with the characteristic 

 pattern on their surface but do not liberate antibody-type 

 globulin. In the Burnet-Fenner theory, any potentiaHties of 

 antibody production against body components were elimi- 

 nated by the development of tolerance. In the present 

 theory they are more readily disposed of by assuming that — 

 at this particular stage of embryonic life — contact with the 

 corresponding antigen pattern results in the death of the cell. 



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