title: The absence of DNA polymerase kappa does not affect somatic hypermutation of the mouse immunoglobulin heavy chain gene.
abstract: During the immune response to T cell-dependent antigen, somatic hypermutation (SHM) is introduced into immunoglobulin (Ig) genes. The variable region is the target for SHM and it is here that DNA lesions are introduced and mutations are generated. It has been suggested that error-prone DNA polymerase(s) may play an important role in this mutagenesis phase. Recently, DNA polymerase kappa (Polkappa), which belongs to the Y-family of DNA polymerases, was identified. Since a hot spot of SHMs (RGYW motif) is also a hot spot of mutations by human Polkappa, this enzyme was suggested to be an SHM instigator. In order to address the question whether Polkappa is involved in SHM, we immunized Polkappa-deficient mice and analyzed the SHM of the Ig heavy chain gene. We found that the SHM frequency and spectrum were indistinguishable between the Polkappa knockout mice and control mice. These results suggested that Polkappa is not essential for this process.
authors.affiliation: Division of Biosignaling, Research Institute for Biological Science (RIBS), Tokyo University of Science, Yamazaki 2669, Noda Chiba 278-0022, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Shimizu
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shinkai
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ogi
authors.forename: Haruo
authors.initials: H
authors.lastname: Ohmori
authors.forename: Takachika
authors.initials: T
authors.lastname: Azuma
mesh_terms: D000818:Animals; D001483:Base Sequence; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005803:Genes, Immunoglobulin / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000276:immunology*; D000099270:Y-Family DNA Polymerases
chemical_list: D004259:DNA-Directed DNA Polymerase; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; C498613:Polk protein, mouse; D000099270:Y-Family DNA Polymerases