Introduction
The TNFR family includes, among others, TNFR1, TNFR2, Fas, CD40, OX40, 4-1BB, death receptor (DR)3/Wsl-1, DR4, DR5, another TNFR-associated factor (TRAF) receptor (ATAR), osteoprotegerin (OPG), and receptor activator of nuclear factor (NF)-κB (RANK 1 2 3 4 5 6 7 8 9). These receptors share similar extracellular domain architecture of multiple cysteine-rich repeats, each containing ∼40 amino acids with six cysteines 1. The extracellular domains are usually preceded by hydrophobic signal peptides. Soluble receptors could be generated by deleting the transmembrane and intracellular domains. The intracellular domains lack enzymatic activities. The receptors may be divided into two subgroups based on the presence (e.g., TNFR1, Fas, DR3, DR4, DR5) or absence (e.g., TNFR2, CD40, RANK) of death domains within their intracellular domains 10. The receptors generally signal through direct interaction with death domain proteins (e.g., TNFR-associated death domain [TRADD], Fas-associated death domain [FADD], receptor-interacting protein [RIP]) or with TRAF proteins (e.g., TRAF2, TRAF3, TRAF5, and TRAF6), triggering cellular signaling pathways leading to apoptosis, NF-κB activation, and/or c-Jun NH2-terminal kinase (JNK) activation 10.
We and others recently reported that TNF- and apoptosis ligand–related leukocyte expressed ligand 1 (TALL-1)/B lymphocyte stimulator (BlyS)/B cell activating factor belonging to the TNF family (BAFF)/TNF homologue that activates apoptosis, NF-κB, and JNK (THANK) is a novel member of the TNF ligand family involved in B cell proliferation 11 12 13 14 15. TALL-1 is a potent B cell costimulatory factor, and acts by direct binding and by activating its cell surface receptor on B cells. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and hypergammaglobulinemia 11 16. These mice also developed autoimmune lupus-like disease characterized by the presence of autoantibodies and immune complex deposits in the kidney 11 16.
Here, we report expression cloning of a TALL-1 receptor from the human Burkitt's lymphoma RAJI cell line. The receptor is identical to transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), a previously reported TNFR homologue identified through its interaction with CAML 17. Our findings suggest the potential presence of another unique subgroup within the TNFR family.