Decreased frequency of somatic hypermutation and impaired affinity maturation but intact germinal center formation in mice expressing antisense RNA to DNA polymerase zeta

J Immunol. 2001 Jul 1;167(1):327-35. doi: 10.4049/jimmunol.167.1.327.


To examine a role of DNA polymerase zeta in somatic hypermutation, we generated transgenic mice that express antisense RNA to a portion of mouse REV3, the gene encoding this polymerase. These mice express high levels of antisense RNA, significantly reducing the levels of endogenous mouse REV3 transcript. Following immunization to a hapten-protein complex, transgenic mice mounted vigorous Ab responses, accomplished the switch to IgG, and formed numerous germinal centers. However, in most transgenic animals, the generation of high affinity Abs was delayed. In addition, accumulation of somatic mutations in the V(H) genes of memory B cells from transgenic mice was decreased, particularly among those that generate amino acid replacements that enhance affinity of the B cell receptor to the hapten. These data implicate DNA polymerase zeta, a nonreplicative polymerase, in the process of affinity maturation, possibly through a role in somatic hypermutation, clonal selection, or both.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Affinity / genetics*
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Clone Cells
  • DNA-Directed DNA Polymerase / biosynthesis
  • DNA-Directed DNA Polymerase / genetics*
  • Down-Regulation / genetics
  • Germinal Center / enzymology*
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Immunoglobulin Heavy Chains / biosynthesis
  • Immunoglobulin Variable Region / biosynthesis
  • Immunoglobulin lambda-Chains / biosynthesis
  • Immunologic Memory / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation*
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Antisense / antagonists & inhibitors
  • RNA, Antisense / biosynthesis*
  • RNA, Messenger / antagonists & inhibitors
  • RNA, Messenger / biosynthesis
  • Up-Regulation / genetics


  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulin lambda-Chains
  • Nucleic Acid Synthesis Inhibitors
  • RNA, Antisense
  • RNA, Messenger
  • DNA polymerase zeta
  • DNA-Directed DNA Polymerase