Robust immunoglobulin class switch recombination and end joining in Parp9-deficient mice

Eur J Immunol. 2017 Apr;47(4):665-676. doi: 10.1002/eji.201646757. Epub 2017 Feb 22.


To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving poly(ADP-ribose) polymerases Parp1, Parp2, and Parp3 to promote appropriate DNA repair and efficient long-range recombination. The macroParp Parp9, which is overexpressed in certain lymphomas, has been recently implicated in DSB repair, acting together with Parp1. Here, we examine the contribution of Parp9 to the resolution of physiological DSBs incurred during V(D)J recombination and CSR by generating Parp9-/- mice. We find that Parp9-deficient mice are viable, fertile, and do not show any overt phenotype. Moreover, we find that Parp9 is dispensable for B-cell development. Finally, we show that CSR and DNA end-joining are robust in the absence of Parp9, indicating that Parp9 is not essential in vivo to achieve physiological DSB repair, or that strong compensatory mechanisms exist.

Keywords: ADP-ribosylation; Antibody diversification; Class switch recombination; DNA repair; Parp9.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Animals
  • B-Lymphocytes / physiology*
  • Cells, Cultured
  • DNA Breaks, Double-Stranded
  • DNA Damage
  • DNA End-Joining Repair*
  • DNA Repair
  • Immunoglobulin Class Switching*
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Poly (ADP-Ribose) Polymerase-1 / metabolism*
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*


  • Immunoglobulins
  • Parp9 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases