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. 2004 Apr 15;103(8):3058-64.
doi: 10.1182/blood-2003-08-2972. Epub 2003 Dec 30.

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  1 , Moritz Wagner, Julia Battiany, Simon Rothenfusser, Daniela Wellisch, Veit Hornung, Bernd Jahrsdorfer, Thomas Giese, Stefan Endres, Gunther Hartmann
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Free article

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 et al. Blood. .
Free article

Abstract

It has been reported that interferon alpha (IFN-alpha) enhances humoral immunity and that dendritic cells of the myeloid lineage promote B-cell differentiation. Here we studied whether the plasmacytoid dendritic cell (PDC), a subset of dendritic cells specialized for the production of IFN-alpha, 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 PDCs via Toll-like receptor 9 (TLR9). The presence of PDCs synergistically enhanced CD86 expression, cytokine production (interleukin 6 [IL-6], tumor necrosis factor alpha, and IL-10) and plasma cell differentiation of isolated human peripheral blood B cells stimulated through CpG-C and B-cell antigen receptor (BCR) ligation. This stimulation protocol was sufficient to drive purified naive B cells into IgM-producing plasma cells and to trigger IgG synthesis in memory B cells. PDCs contributed to B-cell activation via IFN-alpha secretion. Up-regulation of TLR9 on B cells was not involved. These results demonstrate that CpG-stimulated PDCs 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 oligonucleotides as a humoral vaccine adjuvant.

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