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Blood, 15 April 2004, Vol. 103, No. 8, pp. 3058-3064.
Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-08-2972.

Submitted August 29, 2003
Accepted October 31, 2003
Plasmacytoid dendritic cells, antigen and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T cell help
Hendrik Poeck, Moritz Wagner, Julia Battiany, Simon Rothenfusser, Daniela Wellisch, Veit Hornung, Bernd Jahrsdorfer, Thomas Giese, Stefan Endres, and Gunther Hartmann*
Dpt. Internal Medicine, Div. Clinical Pharmacology, Ludwig-Maximians-University of Munich, Munich, Germany
Institute of Immunology, University of Heidelberg, Heidelberg, Germany
* Corresponding author; email: ghartmann{at}lrz.uni-muenchen.de.
It has been reported that IFN- enhances humoral immunity, and that dendritic cells of the myeloid lineage promote B cell differentiation. Here we sought to study whether the plasmacytoid dendritic cell (PDC), a subset of dendritic cells specialized for the production of IFN- , is involved in regulating B cell differentiation and immunoglobulin production. The recently identified class of CpG oligonucleotides (CpG-C) was used to activate both B cells and PDC via TLR9. The presence of PDC synergistically enhanced CD86 expression, cytokine production (IL-6, TNF- and IL-10) and plasma cell differentiation of isolated human peripheral blood B cells stimulated through CpG-C and BCR ligation. This stimulation protocol was sufficient to drive purfied naive B cells into IgM-producing plasma cells, and to trigger IgG synthesis in memory B cells. PDC contributed to B cell activation via IFN- secretion. Upregulation of TLR9 on B cells was not involved. These results demonstrate that CpG-stimulated PDC induce plasma cell differentiation in naive and memory B cells in the absence of T cell help providing an explanation for the excellent activity of CpG ODN as a humoral vaccine adjuvant.

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