B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1.
TALL-1 is a recently identified member of the tumor necrosis factor (TNF) family that costimulates B lymphocyte proliferation. Here we show that B cell maturation protein (BCMA), a member of the TNF receptor family that is expressed only by B lymphocytes, specifically binds to TALL-1. A soluble receptor containing the extracellular domain of BCMA blocks the binding of TALL-1 to its receptor on the plasma membrane and inhibits TALL-1-triggered B lymphocyte costimulation. Overexpression of BCMA activates NF-kappaB, and this activation is potentiated by TALL-1. Moreover, BCMA-mediated NF-kappaB activation is inhibited by dominant negative mutants of TNF receptor-associated factor 5 (TRAF5), TRAF6, NF-kappaB-inducing kinase (NIK), and IkappaB kinase (IKK). These data indicate that BCMA is a receptor for TALL-1 and BCMA activates NF-kappaB through a TRAF5-, TRAF6-, NIK-, and IKK-dependent pathway. The identification of BCMA as a NF-kappaB-activating receptor for TALL-1 suggests molecular targets for drug development against certain immunodeficient or autoimmune diseases.
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Department of Immunology, National Jewish Medical and Research Center and University of Colorado School of Medicine, 1400 Jackson Street, K516c, Denver, CO 80206, USA. shuh@njc.org
Johnson
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D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D017931:DNA Primers; D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha