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

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          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).

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          Most cited references 19

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          Chemokines: a new classification system and their role in immunity.

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            Lymphocyte homing and homeostasis.

            The integration and control of systemic immune responses depends on the regulated trafficking of lymphocytes. This lymphocyte "homing" process disperses the immunologic repertoire, directs lymphocyte subsets to the specialized microenvironments that control their differentiation and regulate their survival, and targets immune effector cells to sites of antigenic or microbial invasion. Recent advances reveal that the exquisite specificity of lymphocyte homing is determined by combinatorial "decision processes" involving multistep sequential engagement of adhesion and signaling receptors. These homing-related interactions are seamlessly integrated into the overall interaction of the lymphocyte with its environment and participate directly in the control of lymphocyte function, life-span, and population dynamics. In this article a review of the molecular basis of lymphocyte homing is presented, and mechanisms by which homing physiology regulated the homeostasis of immunologic resources are proposed.
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              CD40 and CD154 in cell-mediated immunity.

              CD40-CD154-mediated contact-dependent signals between B and T cells are required for the generation of thymus dependent (TD) humoral immune responses. CD40-CD154 interactions are however also important in many other cell systems. CD40 is expressed by a large variety of cell types other than B cells, and these include dendritic cells, follicular dendritic cells, monocytes, macrophages, mast cells, fibroblasts, and endothelial cells. CD40- and CD154-knockout mice and antibodies to CD40 and CD154 have helped to elucidate the role of the CD40-CD154 system in immune responses. Recently published studies indicate that CD40-CD154 interactions can influence T cell priming and T cell-mediated effector functions; they can also upregulate costimulatory molecules and activate macrophages, NK cells, and endothelia as well as participate in organ-specific autoimmune disease, graft rejection, and even atherosclerosis. This review focuses on the role of the CD40-CD154 system in the regulation of many newly discovered functions important in inflammation and cell-mediated immunity.
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                Author and article information

                Contributors
                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                4 December 2000
                : 192
                : 11
                : 1545-1552
                Affiliations
                [a ]Molecular Tumor and Immunogenetics, Max-Delbrück Center for Molecular Medicine, 13092 Berlin, Germany
                [b ]Institute of Molecular Immunology, GSF National Research Center for Environment and Health, 81377 München, Germany
                [c ]Institute of Research in Biomedicine, 6500 Belinzona, Switzerland
                Article
                001428
                2193094
                11104797
                © 2000 The Rockefeller University Press
                Categories
                Original Article

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