Characterization of the cis-acting elements required for somatic hypermutation of murine antibody V genes using conventional transgenic and transgene homologous recombination approaches.
We have used conventional transgenic technology and a novel transgene homologous recombination pathway to investigate the cis-acting elements necessary for murine antibody V-gene somatic hypermutation. These studies show that an undefined element 3' of the IgH intronic enhancer is required for VH hypermutation. This element appears not to be the 3' alpha IgH enhancer, at least in its "minimal' form. Elements 5' of the natural VH promoter are not necessary for hypermutation, and this promoter can be replaced by a non-Ig promoter, resulting in a reduction, but not ablation of the rate of hypermutation in the adjacent VH gene. Our analyses provide no support for "gene conversion' models of hypermutation, and support models that propose a role for transcription in hypermutation over purely DNA-based models. Analysis of a CD72/kappa chimeric transgene suggests that all of the factors that influence hypermutation of kappa transgenes have yet to be defined.
Tumas-Brundage
K
K
Department of Microbiology and Immunology, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA.
Vora
K A
KA
Giusti
A M
AM
Manser
T
T
D000818:Animals; D005803:Genes, Immunoglobulin; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D009154:Mutation; D011401:Promoter Regions, Genetic; D011995:Recombination, Genetic; D019076:Transgenes
D007135:Immunoglobulin Variable Region