Mutation Drift and Repertoire Shift in the Maturation of the Immune Response

The halltnark of the immune response is its specificity and the specificity is directly correlated with the affinity of the antigen-antibody interaction. The requirement for high affinity antibodies may be more important than specificity alone, since antibodies are designed to detect soluble antigens which are sometimes capable of inflicting great harm at very low concentrations (e.g. toxins). This may not be required by. or may even be a disadvantage to T-cell responses where the affinity for the ligand involves interactions of the T-cell receptor not only with antigen, but also with other molecules, e.g. those involved in MHC restriction (Yague et al. 1985. Dembic et al. 1986). T cells therefore may not have developed the equivalent of the elaborate mechanism which is the object of this paper. During the course of an antigen-specific immune response, the affinity of the serum increases with time, a phenomenon commonly referred to as maturation of the response (Jerne 1951, Siskind & Benaceraff 1969). Such a maturation results from specific alterations of the structure of the antibody molecules (Steiner & Eisen 1967). What is the precise nature of these alterations, which are the root of the production of high affinity antibodies? There is no doubt that somatic mutation contributes to antibody diversity (Weigert et al. 1970. Bernard et al. 1978, Griffiths et al. 1984). There are many reasons to believe that a mechanism of hypermutation operates within restricted stretches of the DNA to further diversify the genes encoding the antibody molecules (Kim et al. 1981, Gearhart & Bogenhagen 1983). This mutational drift is, however, not the full extent of the change. Major changes in the antibody structures involved result from a shift in the antigen-specific B-cell repertoire over the course of the immune response. In the primary response the most frequent B-cell clones already expressing antibody molecules with a relatively