Abstract
TRANSGENIC animals containing rearranged heavy or light chains are used to study the process of hypermutation, which characterizes the maturation of the antibody response1–3. LK6 mice contain five copies of a transgene coding for a light chain produced in response to the hapten 2-phenyloxazolone4. We have selected hybridomas from secondary responses that express the transgene as the only light chain2. Some of these hybridomas contain transgene copies carrying mutations known to improve antibody affinity5. We have analysed the expression of the five transgene copies in those hybridomas. We report here that the somatic hypermutation process can affect the successful expression of antibody light-chain transgenes. When mutations that improve the antibody affinity appear in one transgene copy, antigenic selection favours cells that downregulate the other copies at multiple levels of gene expression, including examples where nonsense mutations correlate with a drop in messenger RNA level.
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Lozano, F., Rada, C., Jarvis, J. et al. Affinity maturation leads to differential expression of multiple copies of a κ light-chain transgene. Nature 363, 271–273 (1993). https://doi.org/10.1038/363271a0
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DOI: https://doi.org/10.1038/363271a0
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