Selective activation of TACI by syndecan-2

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

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3235-3242
Number of pages8
JournalBlood
Volume107
Issue number8
DOIs
StatePublished - Apr 15 2006

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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