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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7 June 1999
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June 07 1999
BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth
Pascal Schneider,
Pascal Schneider
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
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Fabienne MacKay,
Fabienne MacKay
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
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Véronique Steiner,
Véronique Steiner
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
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Kay Hofmann,
Kay Hofmann
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
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Jean-Luc Bodmer,
Jean-Luc Bodmer
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
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Nils Holler,
Nils Holler
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
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Christine Ambrose,
Christine Ambrose
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
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Pornsri Lawton,
Pornsri Lawton
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
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Sarah Bixler,
Sarah Bixler
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
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Hans Acha-Orbea,
Hans Acha-Orbea
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
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Danila Valmori,
Danila Valmori
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
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Pedro Romero,
Pedro Romero
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
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Christiane Werner-Favre,
Christiane Werner-Favre
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
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Rudolph H. Zubler,
Rudolph H. Zubler
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
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Jeffrey L. Browning,
Jeffrey L. Browning
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
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Jürg Tschopp
Jürg Tschopp
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
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Pascal Schneider,
Fabienne MacKay,
Véronique Steiner,
Kay Hofmann,
Jean-Luc Bodmer,
Nils Holler,
Christine Ambrose,
Pornsri Lawton,
Sarah Bixler,
Hans Acha-Orbea,
Danila Valmori,
Pedro Romero,
Christiane Werner-Favre,
Rudolph H. Zubler,
Jeffrey L. Browning,
Jürg Tschopp
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
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: [email protected]
P. Schneider and F. MacKay contributed equally to this work.
Received:
January 27 1999
Revision Received:
March 17 1999
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1999
J Exp Med (1999) 189 (11): 1747–1756.
Article history
Received:
January 27 1999
Revision Received:
March 17 1999
Citation
Pascal Schneider, Fabienne MacKay, Véronique Steiner, Kay Hofmann, Jean-Luc Bodmer, Nils Holler, Christine Ambrose, Pornsri Lawton, Sarah Bixler, Hans Acha-Orbea, Danila Valmori, Pedro Romero, Christiane Werner-Favre, Rudolph H. Zubler, Jeffrey L. Browning, Jürg Tschopp; BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth . J Exp Med 7 June 1999; 189 (11): 1747–1756. doi: https://doi.org/10.1084/jem.189.11.1747
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