CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry

Ae-Kyung Yi, Ming Chang, David W. Peckham, Arthur M. Krieg, Robert F. Ashman

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Abstract

Isolated murine splenic B cells undergo spontaneous apoptosis. Motifs containing unmethylated CpG dinucleotides in bacterial DNA or in synthetic oligodeoxynucleotides (ODN) are known to activate murine B cells. Now we show that ODN that induce spleen B cell cycle entry also inhibit spontaneous apoptosis in a sequence-specific fashion. Reversal of the CG to GC abolished activity. Methylation of the central cytosine decreased activity. When CpG is preceded by a cytosine or followed by a guanine, activity was abolished. Other substitutions at the same positions had no effect. Dose-response curves for apoptosis protection and G1 entry suggested that a uniform population of ODN recognition sites controlled downstream ODN effects. A CpG ODN with a nuclease-resistant phosphorothioate backbone (S-ODN) was also active, and increased the levels of c-myc, egr-1, c-jun, bcl(XL), and bax mRNA and c- Myc, c-Jun, Bax, and Bcl(XL) protein in spleen B cells. Levels of c-myb, myn, c-Ki-ras, and bcl2 mRNA remained unchanged. When protein synthesis was inhibited, at 16 h ODN-induced cell cycle entry was abolished and apoptosis protection was partially preserved. Under these conditions, c-Myc was still present, but c-Jun and Bcl(XL) were not detected. Our results suggest that CpG containing ODN motifs provide signals for both survival and cell cycle entry. Single base changes determine whether this signal proceeds through a rate-limiting step governing at least two steps in apoptosis (plasma membrane transition, DNA cleavage) and two phases of the cell cycle (G1 and S phase entry). This biologic action is associated with increased c-Myc, c-Jun, and Bcl(XL) expression.

Original languageEnglish (US)
Pages (from-to)5898-5906
Number of pages9
JournalJournal of Immunology
Volume160
Issue number12
StatePublished - Jun 15 1998

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Oligodeoxyribonucleotides
Cell Cycle
B-Lymphocytes
Spleen
Apoptosis
Cytosine
bcl-X Protein
Bacterial DNA
Messenger RNA
DNA Cleavage
Guanine
G1 Phase
S Phase
Methylation
Cell Membrane
Population

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry. / Yi, Ae-Kyung; Chang, Ming; Peckham, David W.; Krieg, Arthur M.; Ashman, Robert F.

In: Journal of Immunology, Vol. 160, No. 12, 15.06.1998, p. 5898-5906.

Research output: Contribution to journalArticle

Yi, Ae-Kyung ; Chang, Ming ; Peckham, David W. ; Krieg, Arthur M. ; Ashman, Robert F. / CpG oligodeoxyribonucleotides rescue mature spleen B cells from spontaneous apoptosis and promote cell cycle entry. In: Journal of Immunology. 1998 ; Vol. 160, No. 12. pp. 5898-5906.
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