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

• Published in: Blood Vol. 103; no. 8; pp. 3058 - 3064
• Main Authors: Poeck, Hendrik, Wagner, Moritz, Battiany, Julia, Rothenfusser, Simon, Wellisch, Daniela, Hornung, Veit, Jahrsdorfer, Bernd, Giese, Thomas, Endres, Stefan, Hartmann, Gunther
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.04.2004; The Americain Society of Hematology
• Subjects: Antigens - metabolism; B-Lymphocytes - cytology; B-Lymphocytes - immunology; Base Sequence; Biological and medical sciences; Cell Differentiation; CpG Islands; Dendritic Cells - immunology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunoglobulin G - biosynthesis; Immunoglobulin M - biosynthesis; Immunoglobulins - biosynthesis; Immunologic Memory; In Vitro Techniques; Interferon-alpha - biosynthesis; Lymphocyte Activation; Modulation of the immune response (stimulation, suppression); Plasma Cells - cytology; Plasma Cells - immunology; T-Lymphocytes, Helper-Inducer - immunology; Human; Dendritic cell; Immunoglobulins; Alpha interferon; Helper cell; B-Lymphocyte; Plasmocyte; Cell differentiation; Toll like receptor 9; Antigen; GC rich sequence; Antigen presenting cell; T-Lymphocyte; Oligonucleotide; Biological receptor
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-08-2972

It has been reported that interferon α (IFN-α) 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-α, 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 α, 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-α 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)