Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells

Laura L. Stunz, Petar Lenert, David Peckham, Ae-Kyung Yi, Sokol Haxhinasto, Ming Chang, Arthur M. Krieg, Robert F. Ashman

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Reaction to certain motifs in bacterial DNA is an important function of natural immunity. For example, single stranded oligonucleotides (ODN) containing the motif "not C, unmethylated C, G, not G" are powerful mitogens and apoptosis inhibitors for mouse spleen B cells. But replacing GCGTT or ACGTT with GCGGG or ACGGG converted a stimulatory 15-mer ODN into an inhibitory ODN. All inhibitory ODN had three consecutive G, and a fourth G increased inhibitory activity, but a deazaguanosine substitution to prevent planar stacking did not affect activity. Inhibitory ODN blocked apoptosis protection and cell-cycle entry induced by stimulatory ODN, but not that induced by lipopolysaccharide, anti-CD40 or anti-IgM+IL-4. ODN-driven up-regulation of cyclin D2, c-Myc, c-Fos, c-Jun and BclXL and down-regulation of cyclin kinase inhibitor p27kip1 were all blocked by inhibitory ODN. The relative potency of a series of stimulatory and inhibitory ODN was the same for all readouts measured. Interference with uptake of stimulatory ODN could not account for their inhibitory effects. Even if addition of inhibitory ODN was delayed several hours, partial inhibition of stimulatory ODN effects occurred. Inhibitory ODN hold potential as antidotes for excessive ODN stimulation in the clinical setting and provide an important tool for studying ODN recognition.

Original languageEnglish (US)
Pages (from-to)1212-1222
Number of pages11
JournalEuropean Journal of Immunology
Volume32
Issue number5
DOIs
StatePublished - Jun 3 2002

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Oligonucleotides
B-Lymphocytes
Cyclin D2
Apoptosis
Bacterial DNA
Antidotes
Cyclins
Mitogens
Innate Immunity
Interleukin-4
Lipopolysaccharides
Cell Cycle
Phosphotransferases
Up-Regulation
Down-Regulation
Spleen
anti-IgM

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. / Stunz, Laura L.; Lenert, Petar; Peckham, David; Yi, Ae-Kyung; Haxhinasto, Sokol; Chang, Ming; Krieg, Arthur M.; Ashman, Robert F.

In: European Journal of Immunology, Vol. 32, No. 5, 03.06.2002, p. 1212-1222.

Research output: Contribution to journalArticle

Stunz, Laura L. ; Lenert, Petar ; Peckham, David ; Yi, Ae-Kyung ; Haxhinasto, Sokol ; Chang, Ming ; Krieg, Arthur M. ; Ashman, Robert F. / Inhibitory oligonucleotides specifically block effects of stimulatory CpG oligonucleotides in B cells. In: European Journal of Immunology. 2002 ; Vol. 32, No. 5. pp. 1212-1222.
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