Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota.

Somatic hypermutation of immunoglobulin genes is a unique, targeted, adaptive process. While B cells are engaged in germinal centres in T-dependent responses, single base substitutions are introduced in the expressed V[sub H]/V[sub L] genes to allow the selection of mutants with a higher affinity for the immunizing antigen. Almost every possible DNA transaction has been proposed to explain this process, but each of these models includes an errorprone DNA synthesis step that introduces the mutations. The Y family of DNA polymerases—pol η, pol ι, pol κ and rev1—are specialized for copying DNA lesions and have high rates of error when copying a normal DNA template. By performing gene inactivation in a Burkitt's lymphoma cell line inducible for hypermutation, we show here that somatic hypermutation is dependent on DNA polymerase iota. [ABSTRACT FROM AUTHOR]