ANTIBODIES II 31 



enters the circulation, it combines with those molecules which happen 

 to have the corresponding specificity. These combinations are phago- 

 cyted and transported to the antibody-forming cells. There the antigen 

 is dissociated and probably discarded, and the cell — for reasons not 

 specified — proceeds to make more globulin molecules like those just 

 introduced. The casting ofif into the circulation of these new specific 

 globulins constitutes the phenomenon of antibody rise. 



Jerne's theory, in spite of having been proposed only recently, 

 has found considerable favor. Talmage (1957, 1959) considers it 

 essentially similar to the theory of Ehrlich but suggests that the 

 replicating elements are cells rather than extracellular protein. Bur- 

 net (1957) and Lederberg (1959) also support the theory. According 

 to Burnet, antigen combines with specific receptors on the surface 

 of lymphocytes and thereby stimulates these particular cells to settle 

 down and multiply in an appropriate tissue. The result of this 

 replication of selected cells is the production of more of the type of 

 globulin molecule with which the antigen combined in the first place. 



Burnet and Lederberg both assume that the antibody-forming cells 

 are "hypermutable," i.e., that normally there are frequent changes in 

 the types of globulin molecules a cell is genetically capable of pro- 

 ducing. Thus, all possible types of gamma globulin molecules would 

 generally be represented in the circulation zinth the exception of those 

 produced by those cells that happened to combine with antigen while 

 they were still immature ; this is supposed to result in the elimina- 

 tion of such cells. This additional assumption is made to account for 

 the nonproduction of antibodies to antigens of the body itself and for 

 "acquired immunological tolerance."* 



Any attempt to revive the Ehrlich theory must take account of 

 the objection that antibodies can be formed to antigens for which 

 the body can hardly be expected to have preformed natural receptors. 

 Talmage (1959) tries to do this by supposing that sharp specificity, 

 when observed, results from a mixture of globulin molecules, not all 

 alike, each with some degree of specificity for the antigen or hapten. 

 With the help of a diagram (Fig. 2-13) and by thermodynamic calcu- 

 lations he tries to show how the "information" and net specificity of 



* When animals are injected with an antigen during fetal life, or in some 

 cases shortly after birth, they may be incapable of responding immunologically 

 to this antigen as adults (see Chapter 3). 



