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The Journal of Immunology, Vol 157, Issue 11 4918-4925, Copyright © 1996 by American Association of Immunologists
ARTICLES |
AK Yi, P Hornbeck, DE Lafrenz and AM Krieg
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
One of the principal mechanisms thought to maintain B cell tolerance to self Ags is deletion of cells bearing functional IgM receptors for self Ag via apoptosis in the bone marrow. Because of its characteristic growth arrest and apoptosis in response to surface IgM cross-linking, the B cell line WEHI-231 has been a useful model system for studies of Ag receptor-mediated apoptosis. Unmethylated CpG dinucleotides in oligonucleotides (CpG DNA) can be strong B cell mitogens. In the present study we evaluated whether CpG DNA can rescue WEHI-231 cells from anti-IgM-induced cell cycle arrest and apoptosis. The addition of CpG DNA protected WEHI-231 cells from anti-IgM-mediated apoptosis as well as growth arrest. The protective effect of CpG DNA was dependent on the presence of unmethylated CpG dinucleotides. Kinetic analyses showed that the addition of CpG DNA can be delayed for up to 3 h after anti-IgM treatment with no decrease in the protection. CpG DNA reversed anti-IgM-induced down-regulation of c-myc expression in WEHI-231 and up- regulated myn, bcl2, and bcl-xL mRNA expression. Our results suggest that CpG DNA protection of WEHI-231 cells from anti-IgM-induced apoptosis may be mediated by specific and/or cooperative interactions of multiple genes and that CpG DNA could be a useful tool for studies of B cell tolerance.
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A.-K. Yi, M. Chang, D. W. Peckham, A. M. Krieg, and R. F. Ashman CpG Oligodeoxyribonucleotides Rescue Mature Spleen B Cells from Spontaneous Apoptosis and Promote Cell Cycle Entry J. Immunol., June 15, 1998; 160(12): 5898 - 5906. [Abstract] [Full Text] [PDF]
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A.-K. Yi, R. Tuetken, T. Redford, M. Waldschmidt, J. Kirsch, and A. M. Krieg CpG Motifs in Bacterial DNA Activate Leukocytes Through the pH-Dependent Generation of Reactive Oxygen Species J. Immunol., May 15, 1998; 160(10): 4755 - 4761. [Abstract] [Full Text] [PDF]
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A.-K. Yi and A. M. Krieg CpG DNA Rescue from Anti-IgM-Induced WEHI-231 B Lymphoma Apoptosis via Modulation of I{kappa}B{alpha} and I{kappa}B{beta} and Sustained Activation of Nuclear Factor-{kappa}B/c-Rel J. Immunol., February 1, 1998; 160(3): 1240 - 1245. [Abstract] [Full Text] [PDF]
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H. L. Davis, R. Weeranta, T. J. Waldschmidt, L. Tygrett, J. Schorr, and A. M. Krieg CpG DNA Is a Potent Enhancer of Specific Immunity in Mice Immunized with Recombinant Hepatitis B Surface Antigen J. Immunol., January 15, 1998; 160(2): 870 - 876. [Abstract] [Full Text] [PDF]
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