The Journal of Experimental Medicine
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Published online 3 July 2000.
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© The Rockefeller University Press, 0022-1007/2000/7/129/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 1, July 3, 2000 129-136

Brief Definitive Reports

BAFF Binds to the Tumor Necrosis Factor Receptor–like Molecule B Cell Maturation Antigen and Is Important for Maintaining the Peripheral B Cell Population

Jeffrey S. Thompsona, Pascal Schneiderd, Susan L. Kalledb, LiChun Wangb, Eric A. Lefevree, Teresa G. Cacheroc, Fabienne MacKayf, Sarah A. Bixlera, Mohammad Zafarib, Zhong-Ying Liub, Stephen A. Woodcockb, Fang Qianc, Marcel Battenf, Christine Madrye, Yolande Richarde, Christopher D. Benjaminb, Jeffrey L. Browningb, Andreas Tsapise, Jurg Tschoppd, and Christine Ambrosea
a Department of Molecular Genetics, Biogen, Incorporated, Cambridge, Massachusetts 02142
b Department of Immunology and Inflammation, Biogen, Incorporated, Cambridge, Massachusetts 02142
c Department of Protein Engineering, Biogen, Incorporated, Cambridge, Massachusetts 02142
d Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland
e Institut National de la Santé et de la Recherche Médicale U131, 92140 Clamart, France
f Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst NSW 2010, Australia

Correspondence to: Christine Ambrose, Biogen, Inc., 12 Cambridge Center, Cambridge, MA 02142. Tel:617-679-3340 Fax:617-679-2304 E-mail:christine_ambrose{at}biogen.com.

The tumor necrosis factor (TNF) family member B cell activating factor (BAFF) binds B cells and enhances B cell receptor–triggered proliferation. We find that B cell maturation antigen (BCMA), a predicted member of the TNF receptor family expressed primarily in mature B cells, is a receptor for BAFF. Although BCMA was previously localized to the Golgi apparatus, BCMA was found to be expressed on the surface of transfected cells and tonsillar B cells. A soluble form of BCMA, which inhibited the binding of BAFF to a B cell line, induced a dramatic decrease in the number of peripheral B cells when administered in vivo. Moreover, culturing splenic cells in the presence of BAFF increased survival of a percentage of the B cells. These results are consistent with a role for BAFF in maintaining homeostasis of the B cell population.

Key Words: tumor necrosis factor, B lymphocyte, receptor, cell survival, homeostasis


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