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      BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth

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          Abstract

          Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M–stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center–like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.

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          Most cited references 33

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          The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death.

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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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              The pathophysiology of tumor necrosis factors.

               P Vassalli (1991)
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                Author and article information

                Journal
                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                0022-1007
                1540-9538
                7 June 1999
                : 189
                : 11
                : 1747-1756
                Affiliations
                From the [* ]Institute of Biochemistry, University of Lausanne and []Swiss Institute for Experimental Cancer Research, BIL Research Centre, CH-1066 Epalinges, Switzerland; the [§ ]Division for Clinical Onco-Immunology, Ludwig Institute for Cancer Research, CHUV, CH-1011 Lausanne, Switzerland; the []Division of Haematology, Geneva University Hospital, CMU, 1211 Geneva 14, Switzerland; and []Biogen, Inc., Department of Immunology and Inflammation, Cambridge, Massachusetts 02142
                Author notes

                Address correspondence to Jürg Tschopp, Institute of Biochemistry, University of Lausanne, Ch. des Boveresses 155, CH-1066 Epalinges, Switzerland. Phone: 41-21-692-5738; Fax: 41-21-692-5705; E-mail: jurg.tschopp@ 123456ib.unil.ch

                Article
                2193079
                10359578
                Categories
                Articles

                Medicine

                tumor necrosis factor, b lymphocytes, t lymphocytes, b cell growth, immunoglobulin g

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