Somatic hypermutation of immunoglobulin Kappa may depend on sequences 3' of C sub( Kappa ) and occurs on passenger transgenes

We have compared the pattern of somatic mutation in different immunoglobulin Kappa transgenes and suggest that an element(s) located between 1 kb and 9 kb 3' of C sub( Kappa ) is necessary for somatic hypermutation of the antibody V gene. The sequences of transgenic and endogenous Ig V regions were determined in antigen-specific B cell hybridomas specific for 2-phenyloxazolone from independent lines of hyperimmunized transgenic mice. We analysed somatic mutation of the transgene both in hybridomas in which the transgenic Kappa chain contributes to the antigen combining site as well as in hybridomas in which the transgene is a passenger with the expressed antibody being composed of endogenously-encoded heavy and light chains. In both cases, nucleotide changes in the transgene are correctly targeted to the V region and are absent from the C region.