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

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 apopt...

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Bibliographic Details
Published in:International immunology 2003-05, Vol.15 (5), p.577-591
Main Authors: Yi, Ae‐Kyung, Yoon, Jae‐Geun, Krieg, Arthur M.
Format: Article
Language:English
Subjects:
apoptosis
B Lymphocyte
BCR
CpG DNA
cytokine
protein kinase
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Summary: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‐mediated 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.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxg058