title: Human B cell responses to TLR ligands are differentially modulated by myeloid and plasmacytoid dendritic cells.
abstract: Selected TLR ligands are under evaluation as vaccine adjuvants and are known to activate dendritic cells (DCs) and B cells to affect vaccine-induced Ab responses. However, the relative contribution of the two main human DC subsets, myeloid (MDCs) and plasmacytoid (PDCs), in supporting B cell responses to TLR ligands remains poorly understood. We found that PDCs but not MDCs markedly enhanced B cell proliferation in response to TLR7/8-L, an imidazoquinoline derivative, and to a lesser extent to TLR9 ligands (CpG ODN classes A, B, and C). PDCs strongly enhanced TLR7/8-L-induced proliferation of both memory and naive B cells but were only able to support memory cells to differentiate to CD27(high) plasmablasts. In response to TLR7/8 stimulation, PDCs mediated the up-regulation of transcription factors B lymphocyte-induced maturation protein 1 and X-box binding protein 1 and enhanced differentiation of B cells into IgM-, IgG-, and IgA-producing cells. Type I IFN produced to high levels by PDCs was the principal mediator of the effects on TLR7/8 stimulation. Although MDCs expressed higher levels of the known B cell growth factors IL-6, IL-10, and B cell-activating factor in response to TLR7/8 stimulation, they were unable to enhance B cell responses in this system. These data help decipher the different roles of PDCs and MDCs for modulating human B cell responses and can contribute to selection of specific TLR ligands as vaccine adjuvants.
authors.affiliation: Swedish Institute for Infectious Disease Control, Stockholm, Sweden. iyadh.douagi@ki.se
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: Cornelia
authors.initials: C
authors.lastname: Gujer
authors.forename: Christopher
authors.initials: C
authors.lastname: Sundling
authors.forename: William C
authors.initials: WC
authors.lastname: Adams
authors.forename: Anna
authors.initials: A
authors.lastname: Smed-Sörensen
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.forename: Gunilla B
authors.initials: GB
authors.lastname: Karlsson Hedestam
authors.forename: Karin
authors.initials: K
authors.lastname: Loré
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000276:immunology*
chemical_list: D008024:Ligands; D051193:Toll-Like Receptors; D007371:Interferon-gamma