B cell maturation protein is a receptor for the tumor necrosis factor family member TALL-1

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Abstract
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-κB, and this activation is potentiated by TALL-1. Moreover, BCMA-mediated NF-κB activation is inhibited by dominant negative mutants of TNF receptor-associated factor 5 (TRAF5), TRAF6, NF-κB-inducing kinase (NIK), and IκB kinase (IKK). These data indicate that BCMA is a receptor for TALL-1 and BCMA activates NF-κB through a TRAF5-, TRAF6-, NIK-, and IKK-dependent pathway. The identification of BCMA as a NF-κB-activating receptor for TALL-1 suggests molecular targets for drug development against certain immunodeficient or autoimmune diseases.