162 THE BIOSYNTHESIS OF PROTEINS 



of a heterogeneous population of cells with various protein synthesis 

 abilities; this heterogeneity arises in the course of development and 

 differentiation. There are a certain number of different clones (i.e. classes 

 of cells all derived from one single cell by mitotic divisions) which are 

 each competent towards a certain antigenic determinant. If the relevant 

 determinant comes in contact with such a cell, it stimulates this to pro- 

 liferate into plasma cells which produce the corresponding antibodies. It is 

 further assumed that if an antigen reacts with the cell at a certain early 

 stage of differentiation, that cell is functionally eliminated. This would 

 account for the elimination of cells able to produce antibodies against 

 antigenic substances present in the host or introduced into it during early 

 life. One should eventually obtain a residual population of clones able to 

 react only with foreign antigens. 



The fact that different cells often specialize in the production of one or 

 the other antibody (Nossal and Lederberg, 1958) is certainly in line with a 

 selection theory in which the selective process operates at the cellular level. 

 The observation that certain cells can produce two antibodies simultane- 

 ously (Attardi et ah, 1959) conflicts with Burnet's theory which in its most 

 extreme form indeed assumes that each antibody is produced by a different 

 clone of cells, but it is not incompatible with the basic idea of the theory, 

 which can easily be readjusted accordingly. 



Lederberg's views (1959) are very similar to Burnet's; it is assumed that 

 the stem line of antibody forming cells is genotypically heterogeneous 

 owing to relatively frequent mutation in the y-globulin gene. An antigen 

 functions by recognizing those cells already competent to produce a globu- 

 lin which reacts with the antigen. These cells are selected in the sense that 

 they are stimulated to proliferate; on the other hand, their particular 

 ability to produce antibody is also stimulated, or allowed to express itself. 

 The event which is assumed to cause heterogeneity among the stem cells 

 is mutation of a highly mutable globulin gene. Obviously, a 'cytoplasmic' 

 mutation, or any kind of change which can be clonally transmitted would 

 serve the same purpose (Lederberg, 1959; Schultz, 1959). 



It has been mentioned earlier (p. 139) that in bacteria an adapted state, 

 once it has been established, can be maintained clonally through many 

 generations under conditions which could not cause adaptation (Cohn, 

 1957; Novick and Weiner, 1957); this is due to the special properties of a 

 permease system. A model of antibody formation has been derived from 

 this phenomenon by Monod (1959). In the primary response, the antigen 

 is assumed to induce in certain cells both the antibody and a specific 

 permease or a specific cellular antibody which captures the antigen. The 

 cells which have acquired this specific antigen-capture system will exhibit 

 an increased sensitivity to a further antigen injection since they are now 

 able to concentrate it specifically. If they multiply, this increased sensitivity 



