title: Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production.
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)).
authors: Molecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany.
authors: D
authors: D
authors: Breitfeld
authors: L
authors: L
authors: Ohl
authors: E
authors: E
authors: Kremmer
authors: J
authors: J
authors: Ellwart
authors: F
authors: F
authors: Sallusto
authors: M
authors: M
authors: Lipp
authors: R
authors: R
authors: Förster
mesh_terms: D000917:Antibody Formation; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology; D023201:CD40 Ligand / Q000096:biosynthesis; D002458:Cell Fractionation; D016207:Cytokines / Q000096:biosynthesis; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology; D060889:Inducible T-Cell Co-Stimulator Protein; D007963:Leukocytes, Mononuclear / Q000145:classification / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D018121:Receptors, Cytokine / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000145:classification / Q000276:immunology / Q000378:metabolism*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; C515370:CCR7 protein, human; C095085:CXCR5 protein, human; D016207:Cytokines; C556692:ICOS protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D060889:Inducible T-Cell Co-Stimulator Protein; D054400:Receptors, CCR7; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D016201:Receptors, Lymphocyte Homing; D023201:CD40 Ligand