CXCL13 is an arrest chemokine for B cells in high endothelial venules

  • Naotoshi Kanemitsu
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Yukihiko Ebisuno
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Toshiyuki Tanaka
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Kazuhiro Otani
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Haruko Hayasaka
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Tsuneyasu Kaisho
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Shizuo Akira
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Koko Katagiri
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Tatsuo Kinashi
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Naoya Fujita
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Takashi Tsuruo
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.
  • Masayuki Miyasaka
    From the Laboratory of Immunodynamics, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan; Research Center for Allergy and Immunology, the Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; Department of Molecular Genetics, Kansai Medical University, Osaka, Japan; and the Institute of Molecular and Cellular Biosciences, University of Tokyo, Tokyo, Japan.

Abstract

<jats:title>Abstract</jats:title> <jats:p>Chemokine receptor signaling is critical for lymphocyte trafficking across high endothelial venules (HEVs), but the exact mode of action of individual chemokines expressed in the HEVs is unclear. Here we report that CXCL13, expressed in a substantial proportion of HEVs in both lymph nodes (LNs) and Peyer patches (PPs), serves as an arrest chemokine for B cells. Whole-mount analysis of mesenteric LNs (MLNs) showed that, unlike T cells, B cellsa dhere poorly to the HEVs of CXCL13–/– mice and that B-cell adhesion is substantially restored in CXCL13–/– HEVs when CXCL13 is added to the MLNs by superfusion, as we have previously observed in PP HEVs by intravital microscopy. In vitro, CXCL13 activated the small guanosine triphosphatase (GTPase) Rap1 in B cells, and corroborating this observation, a deficiency of RAPL, the Rap1 effector molecule, caused a significant reduction in shear-resistant B-cell adhesion to intercellular adhesion molecule 1 (ICAM-1). In addition, CXCL13 induced B-cell adhesion to mucosal addressin cell adhesion molecule 1 (MAdCAM-1) by activating α4 integrin. These data identify CXCL13 as an arrest chemokine for B cells in HEVs and show that CXCL13 plays an important role in B-cell entry into not only PPs but also MLNs.</jats:p>

Journal

  • Blood

    Blood 106 (8), 2613-2618, 2005-10-15

    American Society of Hematology

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