CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-κB activation

P. Lenert, L. Stunz, Ae-Kyung Yi, A. M. Krieg, R. F. Ashman

Research output: Contribution to journalArticle

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Abstract

Bacterial DNA and CpG-oligodeoxyribonucleotides (ODN) are powerful B cell activators, inducing apoptosis protection, cell cycle entry, proliferation, costimulatory molecule expression, immunoglobulin (Ig) and interleukin-6 (IL-6) secretion. However, proximal events in B cell activation by ODN are only partially characterized, including the translocation of NF-κB to the nucleus. In this paper, we provide evidence that CpG-ODN-induced cell cycle entry and apoptosis protection are blocked by SN50 or gliotoxin and thus require NF-κB activation. NF-κB activation occurred within 30 minutes of stimulation of murine B cells with a phosphorothioate (S) CpG-ODN and persisted for up to 40 hours, with p50, p65, and c-Rel as the major components. Similar to other NF-κB inducers, CpG-ODN caused an early IκBα and IκBβ degradation plus cleavage of the p50 precursor and subsequent NF-κB nuclear translocation. A group of closely related S-ODN, which specifically blocked CpG-induced B cell activation at submicromolar concentrations, also prevented NF-κB DNA binding and transcriptional activation. These inhibitory S-ODN differed from stimulatory S-ODN by having 2-3 G substitutions in the central motif. As inhibitory S-ODN did not directly interfere with the NF-κB DNA binding but prevented CpG-induced NF-κB nuclear translocation of p50, p65, and c-Rel and blocked p105, IκBα, and IκBβ degradation, we concluded that their putative target must lie upstream of inhibitory kinase (IKK) activation.

Original languageEnglish (US)
Pages (from-to)247-256
Number of pages10
JournalAntisense and Nucleic Acid Drug Development
Volume11
Issue number4
DOIs
StatePublished - Jan 1 2001

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Oligodeoxyribonucleotides
B-Lymphocytes
Chemical activation
Cells
Cell Cycle
Gliotoxin
Apoptosis
Degradation
Bacterial DNA
DNA
Transcriptional Activation
Immunoglobulins
Interleukin-6
Substitution reactions
Phosphotransferases
Molecules

All Science Journal Classification (ASJC) codes

  • Genetics
  • Pharmacology

Cite this

CpG stimulation of primary mouse B cells is blocked by inhibitory oligodeoxyribonucleotides at a site proximal to NF-κB activation. / Lenert, P.; Stunz, L.; Yi, Ae-Kyung; Krieg, A. M.; Ashman, R. F.

In: Antisense and Nucleic Acid Drug Development, Vol. 11, No. 4, 01.01.2001, p. 247-256.

Research output: Contribution to journalArticle

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