Selective activation of TACI by syndecan-2.
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.
Bischof
Daniela
D
Mayo Clinic, Mayo Medical School, Department of Pediatric and Adolescent Medicine, Rochester, MN 55905, USA.
Elsawa
Sherine F
SF
Mantchev
George
G
Yoon
Juhan
J
Michels
Grace E
GE
Nilson
Allan
A
Sutor
Shari L
SL
Platt
Jeffrey L
JL
Ansell
Stephen M
SM
von Bulow
Gotz
G
Bram
Richard J
RJ
D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D053668:Syndecan-1; D053669:Syndecan-2; D053671:Syndecan-4; D053667:Syndecans; D014162:Transfection; D053303:Transmembrane Activator and CAML Interactor Protein
D053265:B-Cell Activation Factor Receptor; D053301:B-Cell Maturation Antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D011509:Proteoglycans; D018124:Receptors, Tumor Necrosis Factor; C508241:SDC1 protein, human; C508245:SDC2 protein, human; C508304:SDC4 protein, human; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans; C108467:TNFRSF13B protein, human; C435926:TNFRSF13C protein, human; C086966:TNFRSF17 protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053669:Syndecan-2