Normal immunoglobulin gene somatic hypermutation in Polκ-Polι double-deficient mice

Somatic hypermutation (SHM) occurs in the variable region of immunoglobulin genes in germinal center B cells where it plays an important role in affinity maturation of the T cell-dependent immune response. Although the precise mechanism of SHM is still unknown, it has been suggested that error-prone DNA polymerases (Pol) are involved in SHM. Polι is a member of the error-prone Y-family of DNA polymerases which exhibit translesion synthesis activity in vitro and are highly mutagenic when replicating on non-damaged DNA templates. In BL2 cell line stimulated to induce SHM, the induction is Polι-dependent. However, in 129-derived strains of mice deficient in Polι, SHM is normal. One possible explanation for this discrepancy is that a Polι deficiency in mice might be compensated for by another error-prone DNA polymerase, such as Polκ, which also belongs to the Y-family of DNA polymerases. Although SHM in Polκ-deficient mice is normal, their deficiency might be compensated for by Polι. In this study, we generated Polκ-Polι double-deficient mice and examined them for SHM. We found that the double-deficient mice had the normal SHM frequency and profile, rendering them indistinguishable from Polκ-deficient mice and thus conclude that Polι and Polκ are dispensable for SHM in mice.