J. Exp. Med., Volume 189, Number 11, June 7, 1999 1747-1756

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

By 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,^¶ and 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

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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• Huang, X., Di Liberto, M., Cunningham, A. F., Kang, L., Cheng, S., Ely, S., Liou, H.-c., MacLennan, I. C. M., Chen-Kiang, S. (2004). Homeostatic cell-cycle control by BLyS: Induction of cell-cycle entry but not G1/S transition in opposition to p18INK4c and p27Kip1. Proc. Natl. Acad. Sci. USA 101: 17789-17794 [Abstract] [Full Text]  
• Rahman, Z. S. M., Manser, T. (2004). B Cells Expressing Bcl-2 and a Signaling-Impaired BAFF-Specific Receptor Fail to Mature and Are Deficient in the Formation of Lymphoid Follicles and Germinal Centers. J. Immunol. 173: 6179-6188 [Abstract] [Full Text]  
• Novak, A. J., Grote, D. M., Stenson, M., Ziesmer, S. C., Witzig, T. E., Habermann, T. M., Harder, B., Ristow, K. M., Bram, R. J., Jelinek, D. F., Gross, J. A., Ansell, S. M. (2004). Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome. Blood 104: 2247-2253 [Abstract] [Full Text]  
• Gatto, D., Ruedl, C., Odermatt, B., Bachmann, M. F. (2004). Rapid Response of Marginal Zone B Cells to Viral Particles. J. Immunol. 173: 4308-4316 [Abstract] [Full Text]  
• He, B., Qiao, X., Cerutti, A. (2004). CpG DNA Induces IgG Class Switch DNA Recombination by Activating Human B Cells through an Innate Pathway That Requires TLR9 and Cooperates with IL-10. J. Immunol. 173: 4479-4491 [Abstract] [Full Text]  
• Stohl, W, Metyas, S, Tan, S-M, Cheema, G S, Oamar, B, Roschke, V, Wu, Y, Baker, K P, Hilbert, D M (2004). Inverse association between circulating APRIL levels and serological and clinical disease activity in patients with systemic lupus erythematosus. Ann Rheum Dis 63: 1096-1103 [Abstract] [Full Text]  
• Shulga-Morskaya, S., Dobles, M., Walsh, M. E., Ng, L. G., MacKay, F., Rao, S. P., Kalled, S. L., Scott, M. L. (2004). B Cell-Activating Factor Belonging to the TNF Family Acts through Separate Receptors to Support B Cell Survival and T Cell-Independent Antibody Formation. J. Immunol. 173: 2331-2341 [Abstract] [Full Text]  
• Chen, G., Peng, S., Zou, M., Xu, H., Xu, D., Wang, J. (2004). Construction and Function of Two Cys146-Mutants with High Activity, Derived from Recombinant Human Soluble B Lymphocyte Stimulator. J Biochem 136: 73-79 [Abstract] [Full Text]  
• Cancro, M. P., Kearney, J. F. (2004). B Cell Positive Selection: Road Map to the Primary Repertoire?. J. Immunol. 173: 15-19 [Abstract] [Full Text]  
• Mayer, G., Boileau, G., Bendayan, M. (2004). Sorting of Furin in Polarized Epithelial and Endothelial Cells: Expression Beyond the Golgi Apparatus. J. Histochem. Cytochem. 52: 567-580 [Abstract] [Full Text]  
• Stohl, W (2004). A therapeutic role for BLyS antagonists. Lupus 13: 317-322 [Abstract]  
• Moreaux, J., Legouffe, E., Jourdan, E., Quittet, P., Reme, T., Lugagne, C., Moine, P., Rossi, J.-F., Klein, B., Tarte, K. (2004). BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood 103: 3148-3157 [Abstract] [Full Text]  
• Castigli, E., Scott, S., Dedeoglu, F., Bryce, P., Jabara, H., Bhan, A. K., Mizoguchi, E., Geha, R. S. (2004). Impaired IgA class switching in APRIL-deficient mice. Proc. Natl. Acad. Sci. USA 101: 3903-3908 [Abstract] [Full Text]  
• Hase, H., Kanno, Y., Kojima, M., Hasegawa, K., Sakurai, D., Kojima, H., Tsuchiya, N., Tokunaga, K., Masawa, N., Azuma, M., Okumura, K., Kobata, T. (2004). BAFF/BLyS can potentiate B-cell selection with the B-cell coreceptor complex. Blood 103: 2257-2265 [Abstract] [Full Text]  
• Huard, B., Arlettaz, L., Ambrose, C., Kindler, V., Mauri, D., Roosnek, E., Tschopp, J., Schneider, P., French, L. E. (2004). BAFF production by antigen-presenting cells provides T cell co-stimulation. Int Immunol 16: 467-475 [Abstract] [Full Text]  
• He, B., Chadburn, A., Jou, E., Schattner, E. J., Knowles, D. M., Cerutti, A. (2004). Lymphoma B Cells Evade Apoptosis through the TNF Family Members BAFF/BLyS and APRIL. J. Immunol. 172: 3268-3279 [Abstract] [Full Text]  

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