The DNA glycosylases Ogg1 and Nth1 do not contribute to Ig class switching in activated mouse splenic B cells

• Published in: PloS one 2012-04, Vol.7 (4), p.e36061-e36061
• Main Authors: Ucher, Anna J, Linehan, Erin K, Teebor, George W, Schrader, Carol E, Stavnezer, Janet
• Format: Article
• Language: English
• Subjects: Analysis; Animals; B cells; B-Lymphocytes - enzymology; B-Lymphocytes - immunology; Biology; c-Myc protein; Carcinogens; Cell activation; Cell cycle; Cell Proliferation; Cells, Cultured; Class switching; Clonal deletion; Cooperation; Deoxyribonuclease (Pyrimidine Dimer) - deficiency; Deoxyribonuclease (Pyrimidine Dimer) - genetics; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded; DNA damage; DNA Glycosylases - deficiency; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA repair; Enzymes; Gene deletion; Gene Knockout Techniques; Genes; Genes, myc; Genetic research; Heavy chains; Hydrolases; Immunoglobulin Class Switching; Immunoglobulin Heavy Chains - genetics; Immunoglobulins; Intermediates; Lymphocyte receptors; Lymphocytes B; Medical schools; Metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Mutation; Myc protein; NTH1 protein; OGG1 protein; Oxygen; Physiological aspects; Physiology; Reactive oxygen species; Real-Time Polymerase Chain Reaction; Recombination, Genetic; Rodents; Spleen; Spleen - cytology; Substrates; Switching; Transcription, Genetic
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0036061

During activation of B cells to undergo class switching, B cell metabolism is increased, and levels of reactive oxygen species (ROS) are increased. ROS can oxidize DNA bases resulting in substrates for the DNA glycosylases Ogg1 and Nth1. Ogg1 and Nth1 excise oxidized bases, and nick the resulting abasic sites, forming single-strand DNA breaks (SSBs) as intermediates during the repair process. In this study, we asked whether splenic B cells from mice deficient in these two enzymes would show altered class switching and decreased DNA breaks in comparison with wild-type mice. As the c-myc gene frequently recombines with the IgH S region in B cells induced to undergo class switching, we also analyzed the effect of deletion of these two glycosylases on DSBs in the c-myc gene. We did not detect a reduction in S region or c-myc DSBs or in class switching in splenic B cells from Ogg1- or Nth1-deficient mice or from mice deficient in both enzymes.