IgH class switch recombination to IgG1 in DNA-PKcs-deficient B cells

Immunity. 2002 Apr;16(4):607-17. doi: 10.1016/s1074-7613(02)00306-0.

Abstract

To assess the role of the DNA-PKcs nonhomologous DNA end-joining (NHEJ) protein in Ig heavy chain class switch recombination (CSR), we assayed CSR ability of DNA-PKcs-deficient (DP-T) B cells generated via complementation of DP-T mice with Ig heavy chain and light chain knock-in transgenes (DP-T/HC/LC mice). DP-T/HC/LC mice were severely deficient for all serum IgH isotypes except IgM and, unexpectedly, IgG1. Upon appropriate stimulation, DP-T/HC/LC B cells showed normal proliferation, germline C(H) gene transcription, and AID induction, indicating that DNA-PKcs deficiency did not affect cellular events upstream to CSR. Yet, in vitro activated DP-T/HC/LC B cells again underwent switching only to IgG1 and, like wild-type cells, frequently underwent CSR to gamma1 on both chromosomes. We conclude that DNA-PKcs is required for CSR to most C(H) genes but that CSR to gamma1 occurs via a DNA-PKcs-independent mechanism.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Division
  • Cells, Cultured
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Female
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin Constant Regions / genetics
  • Immunoglobulin G / blood
  • Immunoglobulin G / genetics*
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Isotypes
  • Immunoglobulin Light Chains
  • Immunoglobulin M / blood
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Recombination, Genetic

Substances

  • DNA-Binding Proteins
  • Immunoglobulin Constant Regions
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Isotypes
  • Immunoglobulin Light Chains
  • Immunoglobulin M
  • DNA-Activated Protein Kinase
  • Protein-Serine-Threonine Kinases