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Journal of Endotoxin Research, Vol. 10, No. 6, 431-438 (2004)
DOI: 10.1177/09680519040100060901

CpG oligodeoxynucleotides stimulate IFN-{gamma}-inducible protein-10 production in human B cells

Jörg Vollmer

Coley Pharmaceutical GmbH, Langenfeld, Germany

Marion Jurk

Coley Pharmaceutical GmbH, Langenfeld, Germany

Ulrike Samulowitz

Coley Pharmaceutical GmbH, Langenfeld, Germany

Grayson Lipford

Coley Pharmaceutical Group, Inc., Wellesley, Massachusetts, USA

Alexandra Forsbach

Coley Pharmaceutical GmbH, Langenfeld, Germany

Meike Wüllner

Coley Pharmaceutical GmbH, Langenfeld, Germany

Sybille Tluk

Coley Pharmaceutical GmbH, Langenfeld, Germany

Hanna Hartmann

Coley Pharmaceutical GmbH, Langenfeld, Germany

Andrea Kritzler

Coley Pharmaceutical GmbH, Langenfeld, Germany

Christian Müller

Coley Pharmaceutical GmbH, Langenfeld, Germany

Christian Schetter

Coley Pharmaceutical GmbH, Langenfeld, Germany

Arthur M. Krieg

Coley Pharmaceutical Group, Inc., Wellesley, Massachusetts, USA, akrieg{at}coleypharma.com

Several classes of CpG oligodeoxynucleotides (ODNs) with different immune stimulatory profiles were recently identified: the A-, B- and C-classes. In this study, we investigated the CpG-dependent stimulation of IFN-{gamma}-inducible protein 10 (IP-10 or CXCL10) in different human immune cell types. CpG ODNs induced IP-10 in monocytes, pDCs and in B cells. Purified B cells as well as RPMI 8226 cells responded to CpG stimulation by IP-10 production. Treatment with exogenous IFN-{alpha}2b sensitized PBMCs, purified B cells as well as RPMI 8226 cells to respond more efficiently to stimulation with CpG ODNs by IP-10 production. IP-10 signaling could be directly stimulated via TLR9 in CpG-unresponsive HEK293 cells transfected with human TLR9 and an IP-10 reporter construct. Therefore, CpG-mediated IP-10 production is stimulated through IFN-{alpha} in cells that express the IFN-{alpha} receptor, a second pathway for IP-10 induction exists in TLR9-expressing B cells and pDCs where IP-10 is stimulated directly upon CpG-mediated TLR9 signaling. Our data provide a better understanding of the mechanisms through which CpG ODNs induce efficient Th1 responses.

Key Words: B lymphocytes • CpG • IP-10 • TLR9 • type I interferon


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