Targeting of non-Ig sequences in place of the V segment by somatic hypermutation.
Affinity maturation of antibodies is characterized by localized hypermutation of the DNA around the V segment. Here we show, using mice containing single or multiple transgene constructs, that an immunoglobulin V kappa segment can be replaced by human beta-globin or prokaryotic neo or gpt genes without affecting the rate of hypermutation; the V gene itself is not necessary for recruiting hypermutation. The ability to target hypermutation to heterologous genes in vivo could find more general applications in biology.
Yélamos
J
J
Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Klix
N
N
Goyenechea
B
B
Lozano
F
F
Chui
Y L
YL
González Fernández
A
A
Pannell
R
R
Neuberger
M S
MS
Milstein
C
C
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017931:DNA Primers; D029968:Escherichia coli Proteins; D005914:Globins / Q000235:genetics; D006801:Humans; D006825:Hybridomas; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D019868:Kanamycin Kinase; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010430:Pentosyltransferases; D010581:Peyer's Patches / Q000166:cytology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D011506:Proteins; D011993:Recombinant Fusion Proteins / Q000235:genetics
D001426:Bacterial Proteins; D017931:DNA Primers; D029968:Escherichia coli Proteins; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D011506:Proteins; D011993:Recombinant Fusion Proteins; D005914:Globins; D010430:Pentosyltransferases; C071962:Gpt protein, E coli; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase