Synergy between Cpg- or non-CpG DNA and specific antigen for B cell activation

Yiqiang Wang, Arthur M. Krieg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Citations (Scopus)


DNA or oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG DNA) activate antigen-presenting cells and switch on Th1 immunity to antigen. B cells are synergistically activated by CpG DNA in combination with non-physiologic B cell stimulators such as polyclonal mitogen and surface Ig cross-linkers. This study shows the unexpected finding that not only CpG ODN, but also non-CpG and methylated ODN synergize with specific antigen, hen egg lysozyme (HEL), in stimulating HEL-specific B cells to proliferate, to express the early activation marker CD69 and to activate the NF-κB pathway. In vivo, non-CpG and methylated CpG ODN also enhanced anti-HEL antibody production in HEL-immunized mice, with a bias towards the production of Th1-associated isotypes. The synergy with all ODN to enhance B cell immune function was epitope-specific since neither denatured HEL nor other antigens enhanced the ODN effect on HEL-specific B cells. Furthermore, the synergy was independent of whether the ODN backbone was phosphorothioate or phosphodiester, or whether natural vertebrate genomic DNA was used. In all functional analyses, non-CpG and methylated CpG ODN showed lower activity than CpG ODN. These studies demonstrate that the presence of specific physiologic antigen might broaden the spectrum of DNA/ODN that stimulate B cells, with potential implications for the initiation and regulation of normal and pathologic immune responses.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalInternational Immunology
Issue number2
Publication statusPublished - 1 Feb 2003
Externally publishedYes


  • B lymphocyte
  • BCR
  • CpG motif
  • Immunostimulation
  • Oligodeoxynucleotide


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