Der Einfluss von plasmazytoiden dendritischen Zellen und immunstimulatorischer DNA auf B-Zellen des humanen Immunsystems

Poeck, Hendrik (2006): Der Einfluss von plasmazytoiden dendritischen Zellen und immunstimulatorischer DNA auf B-Zellen des humanen Immunsystems. Dissertation, LMU München: Faculty of Medicine

Abstract

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)

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: B cell, PDC, TLR, CpG oligonucleotides, adaptive immunity
• Subjects: 600 Technology, Medicine > 610 Medical sciences and medicine; 600 Technology, Medicine
• Faculties: Faculty of Medicine
• Language: German
• Date of oral examination: 6. July 2006
• 1. Referee: Endres, Stefan
• Signature of the printed copy: 0700/UMD 11667