International Immunology, Vol. 15, No. 2, pp. 223-231,
February 2003
© 2003 Japanese Society for Immunology
Synergy between CpG- or non-CpG DNA and specific antigen for B cell activation
1 Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA 2 Veterans Affairs Medical Center, Iowa City, IA 52246, USA 3 Coley Pharmaceutical Group, Wellesley, MA 02481, USA
Correspondence to: A. M. Krieg, Coley Pharmaceutical Group, 93 Worcester Street, Suite 101, Wellesley, MA 02481, USA. E-mail: akrieg@coleypharma.com
Transmitting editor: P. Kincade
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-
B 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.
Keywords: B lymphocyte, BCR, CpG motif, immunostimulation, oligodeoxynucleotide
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