Der Einfluss von plasmazytoiden dendritischen Zellen und immunstimulatorischer DNA auf B-Zellen des humanen Immunsystems
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vor 18 Jahren
It has been reported that interferon (IFN-) 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-, 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 , 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- 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. (Blood. 2004;103:3058-3064)
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-, 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 , 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- 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. (Blood. 2004;103:3058-3064)
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