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.
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.
Poeck
Hendrik
H
Department of Internal Medicine, Division of Clinical Pharmacology, Ludwig-Maximilians-University of Munich, Germany.
Wagner
Moritz
M
Battiany
Julia
J
Rothenfusser
Simon
S
Wellisch
Daniela
D
Hornung
Veit
V
Jahrsdorfer
Bernd
B
Giese
Thomas
T
Endres
Stefan
S
Hartmann
Gunther
G
D000941:Antigens / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D001483:Base Sequence; D002454:Cell Differentiation; D018899:CpG Islands; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007136:Immunoglobulins / Q000096:biosynthesis*; D007156:Immunologic Memory; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000096:biosynthesis; D008213:Lymphocyte Activation; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins; D016898:Interferon-alpha