HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Data Supplement Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Douagi, I. Articles by Loré, K. Search for Related Content PubMed PubMed Citation Articles by Douagi, I. Articles by Loré, K.

Human B Cell Responses to TLR Ligands Are Differentially Modulated by Myeloid and Plasmacytoid Dendritic Cells¹

Iyadh Douagi^2,*,, Cornelia Gujer^*,, Christopher Sundling^*,, William C. Adams^*,,, Anna Smed-Sörensen^¶, Robert A. Seder, Gunilla B. Karlsson Hedestam^*, and Karin Loré^*,

^* Swedish Institute for Infectious Disease Control, Stockholm, Sweden; Department of Microbiology, Tumor, and Cell Biology and Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892; and ^¶ Genentech, Inc., South San Francisco, CA 94080

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This study was supported by grants from the International AIDS Vaccine Initiative, the Swedish Research Council, the Swedish International Development Cooperation Agency, and Karolinska Institutet.

² Address correspondence and reprint requests to Dr. Iyadh Douagi, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, SE-171 77 Stockholm, Sweden. E-mail address: iyadh.douagi{at}ki.se

³ Abbreviations used in this paper: DC, dendritic cell; MDC, myeloid DC; PDC, plasmacytoid DC; ASC, Ab-secreting cell; ODN, oligodeoxynucleotide; BAFF, B cell-activating factor; Lin, lineage; poly(I:C), polyinosinic:polycytidylic acid; Xbp-1, X-box binding protein 1; Blimp-1, B lymphocyte-induced maturation protein 1; MT, MitoTracker.

⁴ The online version of this article contains supplemental material.