CpG inhibits IgE class switch recombination through suppression of NF kappa B activity, but not through Id2 or Bcl6.
The CpG motif in DNA plays a critical role in immunity via modulating the Th1/Th2 balance. In B cells, CpG-containing oligodeoxynucleotides (CpG ODNs) inhibit IL-4-mediated class switch recombination (CSR) to IgG1 and IgE through inhibition of the germline transcription (GLT) of these isotypes. However, the molecular mechanism of this inhibitory effect remains elusive. We showed here that Id2 and Bcl6, both of which inhibit IgE GLT and CSR, are not involved in this inhibitory pathway. We demonstrated that there is reduced activity of NF kappa B binding to the IgE promoter and a reduction of Irf4 protein in CpG ODN-treated B cells. These data indicate the critical role of NF kappa B and Irf4 in the regulation of IgE CSR through actions downstream of CpG signaling.
Kusunoki
Takashi
T
Department of Pediatrics, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.
Sugai
Manabu
M
Gonda
Hiroyuki
H
Nambu
Yukiko
Y
Nagata-Nakajima
Natsuki
N
Katakai
Tomoya
T
Kusunoki
Mariko
M
Sakamoto
Akemi
A
Tokuhisa
Takeshi
T
Nakahata
Tatsutoshi
T
Yokota
Yoshifumi
Y
Shimizu
Akira
A
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018899:CpG Islands; D004268:DNA-Binding Proteins / Q000378:metabolism*; D007073:Immunoglobulin E; D007134:Immunoglobulin Switch Region / Q000187:drug effects / Q000502:physiology*; D051797:Inhibitor of Differentiation Protein 2; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009841:Oligonucleotides / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D016328:NF-kappa B; D009841:Oligonucleotides; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; D014157:Transcription Factors; D015847:Interleukin-4; D007073:Immunoglobulin E