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.
journal_name
Bloodjournal_title
Bloodauthors
Bischof D,Elsawa SF,Mantchev G,Yoon J,Michels GE,Nilson A,Sutor SL,Platt JL,Ansell SM,von Bulow G,Bram RJdoi
10.1182/blood-2005-01-0256subject
Has Abstractpub_date
2006-04-15 00:00:00pages
3235-42issue
8eissn
0006-4971issn
1528-0020pii
2005-01-0256journal_volume
107pub_type
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