Fiche du document
2018
- doi: 10.3389/fimmu.2018.02698
- issn: 1664-3224
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2018.02698
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/30524439
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1664-3224
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_CF7EAEC93BBA4
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Cutaneous lupus erythematosusCiter ce document
C. Kowalczyk-Quintas et al., « Inhibition of Membrane-Bound BAFF by the Anti-BAFF Antibody Belimumab. », Serveur académique Lausannois, ID : 10.3389/fimmu.2018.02698
Métriques
Partage / Export
Résumé
B cell activating factor of the TNF family (BAFF, also known as BLyS), a cytokine that regulates homeostasis of peripheral B cells, is elevated in the circulation of patients with autoimmune diseases such as systemic lupus erythematosus (SLE). BAFF is synthetized as a membrane-bound protein that can be processed to a soluble form after cleavage at a furin consensus sequence, a site that in principle can be recognized by any of the several proteases of the pro-protein convertase family. Belimumab is a human antibody approved for the treatment of SLE, often cited as specific for the soluble form of BAFF. Here we show in different experimental systems, including in a monocytic cell line (U937) that naturally expresses BAFF, that belimumab binds to membrane-bound BAFF with similar EC50 as the positive control atacicept, which is a decoy receptor for both BAFF and the related cytokine APRIL (a proliferation inducing ligand). In U937 cells, binding of both reagents was only detectable in furin-deficient U937 cells, showing that furin is the main BAFF processing protease in these cells. In CHO cells expressing membrane-bound BAFF lacking the stalk region, belimumab inhibited the activity of membrane-bound BAFF less efficiently than atacicept, while in furin-deficient U937 cells, belimumab inhibited membrane-bound BAFF and residual soluble BAFF as efficiently as atacicept. These reagents did not activate complement or antibody-dependent cell cytotoxicity upon binding to membrane-bound BAFF in vitro. In conclusion, our data show that belimumab can inhibit membrane-bound BAFF, and that BAFF in U937 cells is processed by furin.