Affinity maturation leads to differential expression of multiple copies of a kappa light-chain transgene.
Transgenic animals containing rearranged heavy or light chains are used to study the process of hypermutation, which characterizes the maturation of the antibody response. LK6 mice contain five copies of a transgene coding for a light chain produced in response to the hapten 2-phenyloxazolone. We have selected hybridomas from secondary responses that express the transgene as the only light chain. Some of these hybridomas contain transgene copies carrying mutations known to improve antibody affinity. 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.
Lozano
F
F
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Rada
C
C
Jarvis
J M
JM
Milstein
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity / Q000235:genetics; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA; D015536:Down-Regulation; D017353:Gene Deletion; D005786:Gene Expression Regulation; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006241:Haptens; D006825:Hybridomas; D007145:Immunoglobulin kappa-Chains / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D010081:Oxazolone / Q000031:analogs & derivatives / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015183:Restriction Mapping
D006241:Haptens; D007145:Immunoglobulin kappa-Chains; D012333:RNA, Messenger; C018361:2-phenyloxazolone; D010081:Oxazolone; D004247:DNA