Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs.
We have recently reported that oligodeoxynucleotides (ODN) that contain a CpG dinucleotide flanked by two purines on the 5'-side and two pyrimidines on the 3'-side induce potent B cell proliferation and differentiation. The present study investigates the role of the ODN backbone in determining the magnitude of the lymphocyte stimulation. Phosphorothioate ODN were approximately 2 logs more potent than the same sequence with a phosphodiester backbone. Chimeric ODN in which the 5'- and 3'-ends were modified with nuclease-resistant internucleotide linkages induced widely varying degrees of immune activation depending on the modification. Phosphorodithioate linkages were by far the most potent and induced B cell activation at nanomolar concentrations, approximately 1 log lower than required for the next most potent modification, phosphorothioate. Methylphosphorothioate terminal linkages were slightly more potent than phosphodiester, which were in turn slightly more potent than terminal methylphosphonate-modified ODN.
Krieg
A M
AM
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
Matson
S
S
Fisher
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D017422:Sequence Analysis, DNA
D016376:Oligonucleotides, Antisense