The DNA glycosylases Ogg1 and Nth1 do not contribute to Ig class switching in activated mouse splenic B cells
Ucher, Anna J. ; Linehan, Erin K. ; Teebor, George W. ; Schrader, Carol E. ; Stavnezer, Janet
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Keywords
B-Lymphocytes
Cell Proliferation
Cells, Cultured
DNA Breaks, Double-Stranded
DNA Glycosylases
Deoxyribonuclease (Pyrimidine Dimer)
Gene Knockout Techniques
Genes, myc
*Immunoglobulin Class Switching
Immunoglobulin Heavy Chains
Mice
Mice, Inbred C57BL
Mice, Knockout
Real-Time Polymerase Chain Reaction
Recombination, Genetic
Spleen
Transcription, Genetic
Genetics and Genomics
Immunology and Infectious Disease
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Abstract
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.
Source
PLoS One. 2012;7(4):e36061. doi: 10.1371/journal.pone.0036061. Epub 2012 Apr 20. Link to article on publisher's site