CD103+ CD11b+ mucosal classical dendritic cells initiate long-term switched antibody responses to flagellin

A. Flores-Langarica*, K. Müller Luda, E. K. Persson, C. N. Cook, S. Bobat, J. L. Marshall, M. W. Dahlgren, K. Hägerbrand, K. M. Toellner, M. D. Goodall, D. R. Withers, I. R. Henderson, B. Johansson Lindbom, A. F. Cunningham, W. W. Agace

*Corresponding author for this work

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    Abstract

    Antibody responses induced at mucosal and nonmucosal sites demonstrate a significant level of autonomy. Here, we demonstrate a key role for mucosal interferon regulatory factor-4 (IRF4)-dependent CD103CD11b+(DP), classical dendritic cells (cDCs) in the induction of T-dependent immunoglobulin G (IgG) and immunoglobulin A (IgA) responses in the mesenteric lymph node (MLN) following systemic immunization with soluble flagellin (sFliC). In contrast, IRF8-dependent CD103+ CD11b- (SP) are not required for these responses. The lack of this response correlated with a complete absence of sFliC-specific plasma cells in the MLN, small intestinal lamina propria, and surprisingly also the bone marrow (BM). Many sFliC-specific plasma cells accumulating in the BM of immunized wild-type mice expressed α4β 7+, suggesting a mucosal origin. Collectively, these results suggest that mucosal DP cDC contribute to the generation of the sFliC-specific plasma cell pool in the BM and thus serve as a bridge linking the mucosal and systemic immune system.

    Original languageEnglish
    JournalMucosal Immunology
    Volume11
    Issue number3
    Pages (from-to)681-692
    ISSN1933-0219
    DOIs
    Publication statusPublished - 1 May 2018

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