Follicular B Helper T Cells Express Cxc Chemokine Receptor 5, Localize to B Cell Follicles, and Support Immunoglobulin Production

DOI PDF 被引用文献44件
  • Dagmar Breitfeld
    aMolecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
  • Lars Ohl
    aMolecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
  • Elisabeth Kremmer
    bInstitute of Molecular Immunology, GSF National Research Center for Environment and Health, 81377 München, Germany
  • Joachim Ellwart
    bInstitute of Molecular Immunology, GSF National Research Center for Environment and Health, 81377 München, Germany
  • Federica Sallusto
    cInstitute of Research in Biomedicine, 6500 Belinzona, Switzerland
  • Martin Lipp
    aMolecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
  • Reinhold Förster
    aMolecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany

抄録

<jats:p>Chemokines and their receptors have been identified as major regulators controlling the functional organization of secondary lymphoid organs. Here we show that expression of CXC chemokine receptor 5 (CXCR5), a chemokine receptor required for B cell homing to B cell follicles, defines a novel subpopulation of B helper T cells localizing to follicles. In peripheral blood these cells coexpress CD45RO and the T cell homing CC chemokine receptor 7 (CCR7). In secondary lymphoid organs, CD4+CXCR5+ cells lose expression of CCR7, which allows them to localize to B cell follicles and germinal centers where they express high levels of CD40 ligand (CD40L), a costimulatory molecule required for B cell activation and inducible costimulator (ICOS), a recently identified costimulatory molecule of the CD28 family. Thus, when compared with CD4+CD45RO+CXCR5− cells, CD4+CD45RO+CXCR5+ tonsillar T cells efficiently support the production of immunoglobulin (Ig)A and IgG. In contrast, analysis of the memory response revealed that long-lasting memory cells are found within the CD4+CD45RO+CXCR5− population, suggesting that CXCR5+CD4 cells represent recently activated effector cells. Based on the characteristic localization within secondary lymphoid organs, we suggest to term these cells “follicular B helper T cells” (TFH).</jats:p>

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