Regulation of the Class Switch Recombination

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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 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 NFκB binding to the IgE promoter and a reduction of Irf4 protein in CpG ODN-treated B cells. These data indicate the critical role of NFκB and Irf4 in the regulation of IgE CSR through actions downstream of CpG signaling. Unexpectedly, STAT6 activity was not markedly changed by CpG ODN treatment. These results indicate that CpG signals work in various ways to induce Th1-skewed immune responses involving B cells.