| First Author | Ingold K | Year | 2005 |
| Journal | J Exp Med | Volume | 201 |
| Issue | 9 | Pages | 1375-83 |
| PubMed ID | 15851487 | Mgi Jnum | J:98196 |
| Mgi Id | MGI:3577593 | Doi | 10.1084/jem.20042309 |
| Citation | Ingold K, et al. (2005) Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med 201(9):1375-83 |
| abstractText | B cell activating factor of the tumor necrosis factor (TNF) family (BAFF) and a proliferation-inducing ligand (APRIL) are closely related ligands within the TNF superfamily that play important roles in B lymphocyte biology. Both ligands share two receptors-transmembrane activator and calcium signal-modulating cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA)-that are predominantly expressed on B cells. In addition, BAFF specifically binds BAFF receptor, whereas the nature of a postulated APRIL-specific receptor remains elusive. We show that the TNF homology domain of APRIL binds BCMA and TACI, whereas a basic amino acid sequence (QKQKKQ) close to the NH(2) terminus of the mature protein is required for binding to the APRIL-specific 'receptor.' This interactor was identified as negatively charged sulfated glycosaminoglycan side chains of proteoglycans. Although T cell lines bound little APRIL, the ectopic expression of glycosaminoglycan-rich syndecans or glypicans conferred on these cells a high binding capacity that was completely dependent on APRIL's basic sequence. Moreover, syndecan-1-positive plasma cells and proteoglycan-rich nonhematopoietic cells displayed high specific, heparin-sensitive binding to APRIL. Inhibition of BAFF and APRIL, but not BAFF alone, prevented the survival and/or the migration of newly formed plasma cells to the bone marrow. In addition, costimulation of B cell proliferation by APRIL was only effective upon APRIL oligomerization. Therefore, we propose a model whereby APRIL binding to the extracellular matrix or to proteoglycan-positive cells induces APRIL oligomerization, which is the prerequisite for the triggering of TACI- and/or BCMA-mediated activation, migration, or survival signals. |
