Convergence of CpG DNA- and BCR- mediated signals at the c-Jun N-terminal kinase and NF-κB activation pathways

Regulation by mitogen-activated protein kinases

Ae-Kyung Yi, Jae Geun Yoon, Arthur M. Krieg

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Depending on the experimental model, unmethylated CpG motifs in bacterial DNA or synthetic oligodeoxynucleotides (CpG DNA) either augment or antagonize BCR-induced signals in B cells. CpG DNA synergizes with BCR-induced proliferation and Ig production of mature B cells, but blocks BCR-mediated apoptosis of immature B cells. Here, we demonstrate using a murine B lymphoma cell line WEHI-231, which is a model for immature B lymphocytes, that CpG DNA augments BCR-mediated signals for the activation of mitogen-activated protein kinase (MAPK) kinase (MKK)3, MKK4 and MKK6, and their subsequent downstream effectors c-Jun N-terminal kinase (JNK) and p38, but does not enhance MEK1/2 or extracellular signal-regulated kinase (ERK) activation. CpG DNA- and BCR-medlated signals also synergize for the activation of transcription factors AP-1, NFAT and NF-κB, but not for cAMP-responsive elements binding factor. Synergistic activations of JNK and p38 contribute to the synergistic production of cytokines induced by CpG DNA- and BCR-mediated signals, but have little or no effect on the ability of CpG DNA to protect WEHI-231 cells from anti-IgM-induced growth arrest. In contrast, all three MAPK, JNK, ERK and p38, contribute to the synergistic induction of splenic mature B cell proliferation by CpG DNA and anti-IgM. These results indicate that CpG DNA- and BCR-mediated signals converge at the level of MKK, NF-κB and NFAT activation, and that MAPK have differential regulatory roles for CpG DNA-mediated cytokine production versus cell proliferation in splenic mature B cells and WEHI-231 cells.

Original languageEnglish (US)
Pages (from-to)577-591
Number of pages15
JournalInternational Immunology
Volume15
Issue number5
DOIs
StatePublished - May 1 2003

Fingerprint

JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases
DNA
B-Lymphocytes
B-Lymphoid Precursor Cells
Phosphotransferases
MAP Kinase Kinase 3
Cell Proliferation
Cytokines
Bacterial DNA
Oligodeoxyribonucleotides
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Transcription Factor AP-1
Lymphoma
Theoretical Models
Apoptosis
Cell Line

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Convergence of CpG DNA- and BCR- mediated signals at the c-Jun N-terminal kinase and NF-κB activation pathways : Regulation by mitogen-activated protein kinases. / Yi, Ae-Kyung; Yoon, Jae Geun; Krieg, Arthur M.

In: International Immunology, Vol. 15, No. 5, 01.05.2003, p. 577-591.

Research output: Contribution to journalArticle

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