SOMATIC MUTATION AS A BASIS 



the serological phenomena we are dealing with is perhaps 

 their most obvious feature. 



In many ways the situation in macroglobulinaemia is the 

 one most suitable for consideration from this point of view. 

 The majority of cases show no abnormal response in the 

 AICF test and the serological features are simply those 

 associated with a high concentration of macroglobulin. This is 

 regarded as due to a near-malignant proliferation of mesen- 

 chymal cells, presumably those normally concerned to 

 produce the macroglobulins of normal serum. If this results 

 from somatic mutation, the changes have not been shown to 

 influence the pattern of the globulin produced. In our two 

 cases with high AICF titre an additional mutation or series 

 of mutations must be postulated by which control over the 

 pattern of the macroglobulin produced is wholly or partly 

 lost. It would seem in fact that a randomization of protein 

 pattern may have taken place basically similar to what is 

 postulated by the clonal selection hypothesis as an essential 

 feature of differentiation during normal development. Since 

 other types of mutation have provided actively proliferating 

 clones to produce the macroglobulin, there is no evidence 

 one way or another as to whether contact of a secondarily 

 modified cell with a corresponding determinant will stimulate 

 it to proliferation. 



6. Congenital agammaglobulinaemia 



The normal infant is born with a relatively high propor- 

 tion of maternal antibody (and gamma globulin) in his 

 circulation. This is gradually used up and at two to three 

 months the gamma globulin level is lower than at any other 

 age (Fried and Henley, 1954). Subsequently active pro- 

 duction of gamma globulin is initiated, possibly as a result 

 of the entry of antigenic substances from the environment. 

 There is evidence that in some children the normal response 

 may be delayed (Spain, Bradess and Greenblatt, 1954), with 

 a resulting period of high susceptibility to pyogenic infection. 



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