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Immunity. 2017 Jan 17;46(1):106-119. doi: 10.1016/j.immuni.2016.12.014.

Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses.

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Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA.
Boston University School of Medicine, Boston, MA 02118, USA.
Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10129, USA.
Department of Respiratory, Inflammation and Autoimmunity (RIA), MedImmune LLC, Gaithersburg, MD 20878, USA.
Department of Cancer Biology, MedImmune LLC, Gaithersburg, MD 20878, USA.
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address:


A hallmark of autoimmunity in murine models of lupus is the formation of germinal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate. In the host response to foreign antigens, follicular dendritic cells (FDCs) maintain GCs through the uptake and cycling of complement-opsonized immune complexes. Here, we examined whether FDCs retain self-antigens and the impact of this process in autoantibody secretion in lupus. We found that FDCs took up and retained self-immune complexes composed of ribonucleotide proteins, autoantibody, and complement. This uptake, mediated through CD21, triggered endosomal TLR7 and led to the secretion of interferon (IFN) α via an IRF5-dependent pathway. Blocking of FDC secretion of IFN-α restored B cell tolerance and reduced the amount of GCs and pathogenic autoantibody. Thus, FDCs are a critical source of the IFN-α driving autoimmunity in this lupus model. This pathway is conserved in humans, suggesting that it may be a viable therapeutic target in systemic lupus erythematosus.


CD21; CD35; DAMP; TLR7; autoimmunity; follicular dendritic cells; immune complex; interferon-α; systemic lupus erythematosus

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