Abstract
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" (T(FH)).
MeSH terms
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Antibody Formation*
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / genetics
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B-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / classification
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CD4-Positive T-Lymphocytes / immunology
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CD40 Ligand / biosynthesis
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Cell Fractionation
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Cytokines / biosynthesis
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Germinal Center / cytology
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Germinal Center / immunology
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Humans
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Immunoglobulin A / biosynthesis
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Immunoglobulin G / biosynthesis
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Immunoglobulin M / biosynthesis
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Immunologic Memory / immunology
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Inducible T-Cell Co-Stimulator Protein
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Leukocytes, Mononuclear / classification
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Leukocytes, Mononuclear / immunology
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Lymphoid Tissue / cytology
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Lymphoid Tissue / immunology*
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Receptors, CCR7
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Receptors, CXCR5
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Receptors, Chemokine / biosynthesis*
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Receptors, Chemokine / genetics
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Receptors, Chemokine / immunology
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Receptors, Cytokine / biosynthesis*
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Receptors, Cytokine / genetics
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Receptors, Cytokine / immunology
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Receptors, Lymphocyte Homing / biosynthesis*
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Receptors, Lymphocyte Homing / genetics
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Receptors, Lymphocyte Homing / immunology
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T-Lymphocytes, Helper-Inducer / classification
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T-Lymphocytes, Helper-Inducer / immunology
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T-Lymphocytes, Helper-Inducer / metabolism*
Substances
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Antigens, Differentiation, T-Lymphocyte
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CCR7 protein, human
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CXCR5 protein, human
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Cytokines
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ICOS protein, human
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Immunoglobulin A
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Immunoglobulin G
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Immunoglobulin M
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Inducible T-Cell Co-Stimulator Protein
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Receptors, CCR7
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Receptors, CXCR5
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Receptors, Chemokine
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Receptors, Cytokine
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Receptors, Lymphocyte Homing
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CD40 Ligand