The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/6/1747/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 11, June 7, 1999 1747-1756

Articles

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

Pascal Schneider*, Fabienne MacKay, Véronique Steiner*, Kay Hofmann{ddagger}, 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, and Jürg Tschopp*

From the * Institute of Biochemistry, University of Lausanne and {ddagger} 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

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.

Key Words: tumor necrosis factor • B lymphocytes • T lymphocytes • B cell growth • immunoglobulin G

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{at}ib.unil.ch

P. Schneider and F. MacKay contributed equally to this work.

Abbreviations used: aa, amino acid(s); APRIL, a proliferation inducing ligand; BAFF, B cell activating factor belonging to the TNF family; EST, expressed sequence tag; LT, lymphotoxin; NF, nuclear factor; PNGase F, peptide N-glycanase F; RANKL, receptor activator of NF-{kappa}B ligand; TRAIL, TNF-related apoptosis-inducing ligand; wt, wild-type.


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