A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors.

Détails

Ressource 1Télécharger: 2018 Flap of BAFF.pdf (4201.76 [Ko])
Etat: Serval
Version: Final published version
ID Serval
serval:BIB_46E3DDBA1F92
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors.
Périodique
Nature communications
Auteur(s)
Vigolo M., Chambers M.G., Willen L., Chevalley D., Maskos K., Lammens A., Tardivel A., Das D., Kowalczyk-Quintas C., Schuepbach-Mallepell S., Smulski C.R., Eslami M., Rolink A., Hummler E., Samy E., Fomekong Nanfack Y., Mackay F., Liao M., Hess H., Jiang X., Schneider P.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
23/03/2018
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
1199
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Résumé
The B cell survival factor (TNFSF13B/BAFF) is often elevated in autoimmune diseases and is targeted in the clinic for the treatment of systemic lupus erythematosus. BAFF contains a loop region designated the flap, which is dispensable for receptor binding. Here we show that the flap of BAFF has two functions. In addition to facilitating the formation of a highly active BAFF 60-mer as shown previously, it also converts binding of BAFF to TNFRSF13C (BAFFR) into a signaling event via oligomerization of individual BAFF-BAFFR complexes. Binding and activation of BAFFR can therefore be targeted independently to inhibit or activate the function of BAFF. Moreover, structural analyses suggest that the flap of BAFF 60-mer temporarily prevents binding of an anti-BAFF antibody (belimumab) but not of a decoy receptor (atacicept). The observed differences in profiles of BAFF inhibition may confer distinct biological and clinical efficacies to these therapeutically relevant inhibitors.
Mots-clé
Animals, Antibodies, Monoclonal, Humanized/pharmacology, B-Cell Activating Factor/chemistry, B-Cell Activating Factor/genetics, B-Cell Activating Factor/physiology, B-Cell Activation Factor Receptor/chemistry, B-Lymphocytes/cytology, Cell Differentiation, Cell Survival, Cross-Linking Reagents/chemistry, Female, Gene Knock-In Techniques, HEK293 Cells, Humans, Immunoglobulin Fragments/chemistry, Lymphopenia/metabolism, Male, Mice, Mice, Transgenic, Mutation, Protein Binding, Protein Domains, Recombinant Fusion Proteins/pharmacology
Pubmed
Web of science
Open Access
Oui
Création de la notice
26/03/2018 14:35
Dernière modification de la notice
08/05/2019 17:58
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