Lack of somatic mutation in a kappa light chain transgene.
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 kappa transgene encoding a V region specific for the hapten 2-phenyloxazolone (phOx) linked to a rat C kappa 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 kappa coding region are necessary to direct somatic mutation.
Sharpe
M J
MJ
MRC Laboratory of Molecular Biology, Cambridge, GB.
Neuberger
M
M
Pannell
R
R
Surani
M A
MA
Milstein
C
C
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain / Q000276:immunology*; D006825:Hybridomas / Q000032:analysis; D007114:Immunization; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D010081:Oxazolone / Q000031:analogs & derivatives / Q000276:immunology
D007143:Immunoglobulin Heavy Chains; D007145:Immunoglobulin kappa-Chains; C018361:2-phenyloxazolone; D010081:Oxazolone