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Science 293 (5537): 2108-2111

Copyright © 2001 by the American Association for the Advancement of Science

BAFF-R, a Newly Identified TNF Receptor That Specifically Interacts with BAFF

Jeffrey S. Thompson,1 Sarah A. Bixler,1 Fang Qian,1 Kalpit Vora,1* Martin L. Scott,1 Teresa G. Cachero,1 Catherine Hession,1 Pascal Schneider,2 Irene D. Sizing,1 Colleen Mullen,1 Kathy Strauch,1 Mohammad Zafari,1 Christopher D. Benjamin,1 Jurg Tschopp,2 Jeffrey L. Browning,1 Christine Ambrose1dagger

B cell homeostasis has been shown to critically depend on BAFF, the B cell activation factor from the tumor necrosis factor (TNF) family. Although BAFF is already known to bind two receptors, BCMA and TACI, we have identified a third receptor for BAFF that we have termed BAFF-R. BAFF-R binding appears to be highly specific for BAFF, suggesting a unique role for this ligand-receptor interaction. Consistent with this, the BAFF-R locus is disrupted in A/WySnJ mice, which display a B cell phenotype qualitatively similar to that of the BAFF-deficient mice. Thus, BAFF-R appears to be the principal receptor for BAFF-mediated mature B cell survival.

1 Biogen, 12 Cambridge Center, Cambridge, MA 02142, USA.
2 The Institute of Biochemistry, University of Lausanne, CH-1066, Epalinges, Switzerland.
*   Present address: Department of Biologics Research, Merck & Co., 126 East Lincoln Avenue, RY 80Y-310, Rahway, NJ 07065, USA.

dagger    To whom correspondence should be addressed. E-mail: christine_ambrose{at}

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   Abstract »    Full Text »    PDF »
BAFF controls B cell metabolic fitness through a PKC{beta}- and Akt-dependent mechanism.
A. Patke, I. Mecklenbrauker, H. Erdjument-Bromage, P. Tempst, and A. Tarakhovsky (2006)
J. Exp. Med. 203, 2551-2562
   Abstract »    Full Text »    PDF »
A role for BLyS in the activation of innate immune cells.
S. K. Chang, B. K. Arendt, J. R. Darce, X. Wu, and D. F. Jelinek (2006)
Blood 108, 2687-2694
   Abstract »    Full Text »    PDF »
A BAFF antagonist suppresses experimental autoimmune encephalomyelitis by targeting cell-mediated and humoral immune responses.
N. D. Huntington, R. Tomioka, C. Clavarino, A. M. Chow, D. Linares, P. Mana, J. Rossjohn, T. G. Cachero, F. Qian, S. L. Kalled, et al. (2006)
Int. Immunol. 18, 1473-1485
   Abstract »    Full Text »    PDF »
Paucity of Clinical Disease despite Serological Autoimmunity and Kidney Pathology in Lupus-Prone New Zealand Mixed 2328 Mice Deficient in BAFF.
C. O. Jacob, L. Pricop, C. Putterman, M. N. Koss, Y. Liu, M. Kollaros, S. A. Bixler, C. M. Ambrose, M. L. Scott, and W. Stohl (2006)
J. Immunol. 177, 2671-2680
   Abstract »    Full Text »    PDF »
Aberrant expression of BAFF in T cells of systemic lupus erythematosus, which is recapitulated by a human T cell line, Loucy.
K. Yoshimoto, Y. Takahashi, M. Ogasawara, Y. Setoyama, K. Suzuki, K. Tsuzaka, T. Abe, and T. Takeuchi (2006)
Int. Immunol. 18, 1189-1196
   Abstract »    Full Text »    PDF »
Chronic Administration of Belimumab, a BLyS Antagonist, Decreases Tissue and Peripheral Blood B-Lymphocyte Populations in Cynomolgus Monkeys: Pharmacokinetic, Pharmacodynamic, and Toxicologic Effects.
W. G. Halpern, P. Lappin, T. Zanardi, W. Cai, M. Corcoran, J. Zhong, and K. P. Baker (2006)
Toxicol. Sci. 91, 586-599
   Abstract »    Full Text »    PDF »
Space, Selection, and Surveillance: Setting Boundaries with BLyS..
J. P. Miller, J. E. Stadanlick, and M. P. Cancro (2006)
J. Immunol. 176, 6405-6410
   Abstract »    Full Text »    PDF »
APRIL and BAFF Promote Increased Viability of Replicating Human B2 Cells via Mechanism Involving Cyclooxygenase 2..
P. K. A. Mongini, J. K. Inman, H. Han, R. J. Fattah, S. B. Abramson, and M. Attur (2006)
J. Immunol. 176, 6736-6751
   Abstract »    Full Text »    PDF »
Constitutive NF-{kappa}B and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas.
L. Fu, Y.-C. Lin-Lee, L. V. Pham, A. Tamayo, L. Yoshimura, and R. J. Ford (2006)
Blood 107, 4540-4548
   Abstract »    Full Text »    PDF »
The PANE1 gene encodes a novel human minor histocompatibility antigen that is selectively expressed in B-lymphoid cells and B-CLL.
A. G. Brickner, A. M. Evans, J. K. Mito, S. M. Xuereb, X. Feng, T. Nishida, L. Fairfull, R. E. Ferrell, K. A. Foon, D. F. Hunt, et al. (2006)
Blood 107, 3779-3786
   Abstract »    Full Text »    PDF »
Phospholipase C{gamma}2 Dosage Is Critical for B Cell Development in the Absence of Adaptor Protein BLNK..
S. Xu, J. Huo, W.-K. Chew, M. Hikida, T. Kurosaki, and K.-P. Lam (2006)
J. Immunol. 176, 4690-4698
   Abstract »    Full Text »    PDF »
B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom macroglobulinemia.
S. F. Elsawa, A. J. Novak, D. M. Grote, S. C. Ziesmer, T. E. Witzig, R. A. Kyle, S. R. Dillon, B. Harder, J. A. Gross, and S. M. Ansell (2006)
Blood 107, 2882-2888
   Abstract »    Full Text »    PDF »

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