THEORIES OF ANTIBODY PRODUCTION 



' goodness of fit ' between reactive site and antigenic deter- 

 minant plus the accessibility of the receptors to antigenic 

 determinants under the existing conditions will play a part 

 as well as usual measures of concentration of antigen. 



The family of curves, beginning with the most steeply 

 sloping broken line, is intended to represent immunological 

 reactivity of immunologically conditioned cells at various stages 

 of the process of maturation. It is assumed without proof 

 that curves shown in broken lines would depict eventual 

 destruction of a stimulated cell, while continuous lines 

 represent persistence of the cell line. 



This diagram is of special interest in relation to work on the 

 induction of non-reactivity by administration of a single dose 

 of a pure antigen to rabbits at birth (Smith, 1958). Under 

 these circumstances so long as an appropriate number of 

 antigenic determinants are in contact with a cell, the cell is 

 rendered dormant in two senses: (a) it is incapable of 

 developing into a plasma cell and producing antibody and 

 {b) it remains at the same stage of immaturity as it was at the 

 time of first contact with antigen. 



In any workable form of the clonal selection theory it will 

 be necessary to consider reaction with related patterns. 

 All that is demanded of the primary differentiation or 

 randomization of pattern is that a sufficient number of clones 

 are produced to provide sites with a close enough fit to all 

 possible antigenic determinants to allow some reaction. As 

 long as it is possible by directed protein synthesis to secure 

 a better fit, it is legitimate to look to minor somatic mutation 

 to allow its emergence. 



If, in fact, the concept of randomization of pattern in 

 embryonic life is accepted, or even a complex genetically 

 determined output of multiple globulin patterns arising by 

 differentiation, then it would be in accord with biological 

 probabihties to find an occurrence of relatively frequent 

 (somatic) mutation in the range of loci concerned in this 

 particular function of specifying pattern of gamma globulin. 



66 



