THE COLLAGEN DISEASES 



thing of the nature of a somatic mutation must be postu- 

 lated, but in regard to rheumatic fever and nephritis a definite 

 role must be given to the streptococcus. The specially 

 nephritogenic quality of some types of haemolytic strepto- 

 cocci (for example, Type 12) speaks for a rather specific role. 

 It need not, however, be a mutagenic action. In all our 

 discussions of clonal phenomena, we have two equally im- 

 portant operational factors: the appearance of the appro- 

 priate mutation and the opportunity for selective prolifera- 

 tion of the mutant. Streptococcal infection of the lymphoid 

 tissues of the throat may be mutagenic, but equally it might 

 favour the proliferation of forbidden clones by interfering 

 with some process of control which would normally ensure 

 their elimination. We should favour the second alternative 

 but a decision is not vital. All we are concerned with is the 

 appearance of mutant cells which differ from the normal in 

 being susceptible to immunological stimulation by antigenic 

 determinants present in some normal tissue components. 



Lymphocytes are constantly 'exploring' tissues in most 

 parts of the body and sooner or later one of our hypo- 

 thetical mutant cells will meet the appropriate antigenic 

 determinant. Depending on various circumstances, the 

 cell's reaction to the specific stimulus might be: 



(i) to release histamine and/or other pharmacologically 

 active substances damaging both cell and tissue, 

 or (ii) to initiate proliferation either locally or in reticular 

 tissue, either lymphocytes or plasma cells being 

 produced. 



A second ad hoc assumption which may be necessary is that 

 the commonest determinant involved only becomes acces- 

 sible to wandering cells under conditions of minor trauma or 

 its equivalent. 



It would be unprofitable to follow these hypotheses further 

 until a more direct experimental approach is possible but 

 it is easy to see that they could allow a picture to be built up 

 corresponding reasonably well with the known pathology of 



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