title: Interaction of the TNF homologues BLyS and APRIL with the TNF receptor homologues BCMA and TACI.
abstract: BLyS (also called TALL-1, THANK, or BAFF) [1] [2] [3] [4] is a member of the tumor necrosis factor (TNF) gene family that stimulates proliferation and immunoglobulin production by B cells. BLyS interacts with the TNF receptor (TNFR) homologue TACI (transmembrane activator and CAML-interactor) [5], and treatment of mice with a TACI-Fc fusion protein abolishes germinal center formation after antigenic challenge [6]. Here we report a novel interaction between BLyS and another TNFR homologue, BCMA (B cell maturation antigen) [7] [8]. Further, the TNF homologue APRIL [9], a close relative of BLyS, also bound to BCMA and TACI. BLyS or APRIL activated nuclear factor-kappaB (NF-kappaB) through TACI and BCMA, and each ligand stimulated immunoglobulin M (IgM) production by peripheral blood B cells. These results define a dual ligand-receptor system that may play an important role in humoral immunity.
authors.affiliation: Departments of Molecular Oncology, Genentech, Inc., South San Francisco, CA 94080-4918, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Marsters
authors.forename: M
authors.initials: M
authors.lastname: Yan
authors.forename: R M
authors.initials: RM
authors.lastname: Pitti
authors.forename: P E
authors.initials: PE
authors.lastname: Haas
authors.forename: V M
authors.initials: VM
authors.lastname: Dixit
authors.forename: A
authors.initials: A
authors.lastname: Ashkenazi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011485:Protein Binding; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D017386:Sequence Homology, Amino Acid; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D007075:Immunoglobulin M; D008565:Membrane Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C108467:TNFRSF13B protein, human; C086966:TNFRSF17 protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha