Lack of somatic mutation in a χ light chain transgene

Abstract

Analysis of mice transgenic for immunoglobulin genes should allow definition of the cis‐acting DNA sequences required to target somatic mutation to antibody V genes. We have looked for mutations in a chimeric χ transgene encoding a V region specific for the hapten 2‐phenyloxazolone (phOx) linked to a rat C_χ gene. Two independent lines of transgenic mice were hyperimmunized with phOx and splenic hybridomas established. In B cells that had been selected by antigen and which used mouse anti‐phOx genes, the endogenous sequences were found to be mutated whereas the transgene remained unchanged. These results suggest either that (a) if the transgene is a “passenger” gene expressed at a low level, transgene mutation is a rare event, or that (b)sequences far from the χ coding region are necessary to direct somatic mutation.