Inhibition of Membrane-Bound BAFF by the Anti-BAFF Antibody Belimumab.

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Version: Final published version
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Serval ID
serval:BIB_CF7EAEC93BBA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibition of Membrane-Bound BAFF by the Anti-BAFF Antibody Belimumab.
Journal
Frontiers in immunology
Author(s)
Kowalczyk-Quintas C., Chevalley D., Willen L., Jandus C., Vigolo M., Schneider P.
ISSN
1664-3224 (Electronic)
ISSN-L
1664-3224
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
9
Pages
2698
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Abstract
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.
Keywords
Antibodies, Monoclonal, Humanized/pharmacology, B-Cell Activating Factor/antagonists & inhibitors, B-Cell Activating Factor/immunology, Cell Membrane/immunology, Furin/immunology, HEK293 Cells, Humans, Lupus Erythematosus, Systemic/drug therapy, Lupus Erythematosus, Systemic/immunology, Lupus Erythematosus, Systemic/pathology, Tumor Necrosis Factor Ligand Superfamily Member 13/immunology, U937 Cells, BAFF, BLyS, antibody-dependent cell death, complement, furin, protein shedding
Pubmed
Web of science
Open Access
Yes
Create date
29/11/2018 11:47
Last modification date
04/10/2019 6:08
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