Selective activation of TACI by syndecan-2.

Academic Article


  • B-lymphocyte homeostasis and function are regulated by complementary actions of the TNFR family members TACI, BCMA, and BAFF-R, which are expressed by mature B cells. How these receptors are differentially activated is not entirely understood, because the primary ligand BAFF binds to all three. We searched for alternative ligands for TACI using recombinant TACI-Fc fusion protein as a probe and identified syndecan-2 as a new binding partner. TACI binding appears to require heparan sulfate posttranslational modifications of syndecan-2, because free heparin or pretreatment with heparitinase blocked the interaction. Syndecan-2 bound TACI but bound neither BAFF-R nor BCMA. Transfected cells expressing syndecan-2 activated signaling through TACI, as indicated by an NFAT-specific reporter. Syndecan-1 and syndecan-4 were also able to induce TACI signaling in a similar manner. This is the first identification of ligands that selectively activate TACI without simultaneously triggering BCMA or BAFF-R. This finding may help explain the alternative outcomes of signaling from this family of receptors in B cells.
  • Authors

  • Bischof, Daniela
  • Elsawa, Sherine
  • Mantchev, George
  • Yoon, Juhan
  • Michels, Grace E
  • Nilson, Allan
  • Sutor, Shari L
  • Platt, Jeffrey L
  • Ansell, Stephen M
  • von Bulow, Gotz
  • Bram, Richard J
  • Status

    Publication Date

  • April 15, 2006
  • Published In

  • Blood  Journal
  • Keywords

  • B-Cell Activation Factor Receptor
  • B-Cell Maturation Antigen
  • B-Lymphocytes
  • Gene Expression
  • Humans
  • Jurkat Cells
  • Lymphocyte Activation
  • Membrane Glycoproteins
  • Membrane Proteins
  • NFATC Transcription Factors
  • Proteoglycans
  • Receptors, Tumor Necrosis Factor
  • Signal Transduction
  • Syndecan-1
  • Syndecan-2
  • Syndecan-4
  • Syndecans
  • Transfection
  • Transmembrane Activator and CAML Interactor Protein
  • Digital Object Identifier (doi)

    Start Page

  • 3235
  • End Page

  • 3242
  • Volume

  • 107
  • Issue

  • 8