Somatic mutation and the immune response

Gefter [99] and Milstein [100,101] and their colleagues have extensively studied the ontogeny of the immune responses of A/J mice to Ars and of BALB/c mice to 

2- phenyl-oxazolone (Ox) respectively. In both cases recurrent major idiotypic families of antibodies are elicited by immunization. The time course of expression of structurally related antibodies can therefore be followed by collecting hybridomas from different mice at various times after immunization. Both these groups observe that while the V genes expressed by hydridomas isolated early (days 

The experiments described above do not rule out the formal possibility that some of the observed mutation occurs prior to the immune response in a small fraction of B cells, and that this fraction of cells is then preferentially clonally expanded during an immune response. In this regard, evidence suggesting that somatic mutation may be operative at the pre-B cell stage of differentiation has been obtained [104-106]. 

Due to the lack of direct experimental evidence concerning the mechanism by which somatic nucleotide replacements occur in variable region genes, little can be concluded at present concerning the nature of this mechanism(s). In this section I endeavor to review what has been learned indirectly about this process and discuss how this information bears on the feasibility of a number of models for the generation of mutational diversity. 

In vitro model systems for the study of somatic mutation 

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