AFFINITY MATURATION LEADS TO DIFFERENTIAL EXPRESSION OF MULTIPLE COPIES OF A KAPPA-LIGHT-CHAIN TRANSGENE

TRANSGENIC animals containing rearranged heavy or light chains are use d to study the process of hypermutation, which characterizes the matur ation of the antibody response1-3. LK6 mice contain five copies of a t ransgene coding for a light chain produced in response to the hapten 2 -phenyloxazolone4. We have selected hybridomas from secondary response s that express the transgene as the only light chain2. Some of these h ybridomas contain transgene copies carrying mutations known to improve antibody affinity5. We have analysed the expression of the five trans gene copies in those hybridomas. We report here that the somatic hyper mutation process can affect the successful expression of antibody ligh t-chain transgenes. When mutations that improve the antibody affinity appear in one transgene copy, antigenic selection favours cells that d ownregulate the other copies at multiple levels of gene expression, in cluding examples where nonsense mutations correlate with a drop in mes senger RNA level.