Synergy between CpG- or non-CpG DNA and specific antigen for B cell activation.
DNA or oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG DNA) activate antigen-presenting cells and switch on T(h)1 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-kappaB 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 T(h)1-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.
Wang
Yiqiang
Y
Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242, USA.
Krieg
Arthur M
AM
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002455:Cell Division / Q000502:physiology*; D018899:CpG Islands / Q000502:physiology*; D004247:DNA / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000378:metabolism*
D004247:DNA; C421864:hen egg lysozyme; D009113:Muramidase