Genetically controlled idiotype expression in inbred mice.
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Biomedical subjects
Publications and source records attributed to C Berek.
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The expression of different idiotypic families encountered in the anti-phosphorylcholine antibodies depends on the association of a heavy chain with one of the VL sub-families. Manipulation of the response by idiotypic suppression leads to formation of a T15cr family whose structural correlates are analysed by determination of the mRNA sequence of hybridoma heavy and light chains.
Studies on the development of the immune response suggest that the repertoire of expressed antibody specificities is strongly influenced by antigen (reviewed in ref. 1). One way in which this influence is manifested is by a progressive increase in the affinity of antibody for antigen with time after immunization. This phenomenon, termed the 'maturation' of the immune response, must be due to a change in the structure of the antibody being synthesized. However, the precise nature of the changes involved and the genetic mechanisms used to produce them have not been clearly defined. We have now investigated the maturation of the immune response to the hapten 2-phenyloxazolone by mRNA sequencing of specific hybridomas. We conclude that somatic mutation of germ-line encoded genes plays a major role in the generation of antibodies with increased affinity for oxazolone with time after immunization.
Sequence analysis of the heavy- and light-chain messenger RNA of hybridomas immunized with a specific hapten yields important clues about the interplay between genetic and selective events during the onset and maturation of the immune response. The maturation of the primary response to the hapten 2-phenyl-5-oxazolone is characterized by a drift to higher-affinity somatic variants of a germline-encoded basic sequence, whereas hybridomas from the secondary response demonstrate a further maturation dominated by a shift to alternative germline combinations.