Induction of Somatic Hypermutation in Immunoglobulin Genes Is Dependent on DNA Polymerase Iota

Nature. 2002 Oct 31;419(6910):944-7. doi: 10.1038/nature01117.

Abstract

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 Vh/Vl 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 error-prone DNA synthesis step that introduces the mutations. The Y family of DNA polymerases--pol eta, pol iota, pol kappa 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibody Affinity / genetics
  • B-Lymphocytes / immunology
  • Blotting, Western
  • Burkitt Lymphoma / enzymology
  • Burkitt Lymphoma / genetics
  • Burkitt Lymphoma / immunology
  • Cytidine Deaminase / metabolism
  • DNA-Directed DNA Polymerase / deficiency
  • DNA-Directed DNA Polymerase / genetics
  • DNA-Directed DNA Polymerase / metabolism*
  • Gene Deletion
  • Genes, Immunoglobulin / genetics*
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Molecular Sequence Data
  • Mutation / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Somatic Hypermutation, Immunoglobulin*
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Immunoglobulins
  • RNA, Messenger
  • DNA polymerase iota
  • DNA-Directed DNA Polymerase
  • AICDA (activation-induced cytidine deaminase)
  • Cytidine Deaminase

Associated data

  • GENBANK/AC021325