title: Analysis of a T cell receptor gene as a target of the somatic hypermutation mechanism.
abstract: In an effort to identify cis-acting elements required for targeting of the somatic hypermutation process in mice, we examined whether a T cell receptor (TCR) transgene under the control of the immunoglobulin (Ig) heavy (H) chain intron enhancer would be mutated in antigen-stimulated B cells. Hybridomas were established from splenic B cells of mice carrying two copies of the TCR transgene after hyperimmunization with phosphorylcholine keyhole limpet hemocyanin. Northern analysis revealed that all of the transgene-containing hybridomas expressed the TCR mRNA. Multiple somatic point mutations were found in seven of eight endogenous Ig VH genes examined. In contrast, 29 of 32 TCR genes examined contained no mutations. One potential mutation was seen in each of the three other TCR genes. Our data indicate that although the TCR transgene is expressed in B cells, it is not efficiently targeted by the mutator mechanism. Furthermore, the presence of an Ig H chain enhancer is itself not sufficient for targeting of the somatic hypermutation mechanism.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Illinois 60637.
authors.forename: J
authors.initials: J
authors.lastname: Hackett
authors.forename: C
authors.initials: C
authors.lastname: Stebbins
authors.forename: B
authors.initials: B
authors.lastname: Rogerson
authors.forename: M M
authors.initials: MM
authors.lastname: Davis
authors.forename: U
authors.initials: U
authors.lastname: Storb
mesh_terms: D000818:Animals; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D011948:Receptors, Antigen, T-Cell