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dc.contributor.authorVigolo, M
dc.contributor.authorChambers, MG
dc.contributor.authorWillen, L
dc.contributor.authorChevalley, D
dc.contributor.authorMaskos, K
dc.contributor.authorLammens, A
dc.contributor.authorTardivel, A
dc.contributor.authorDas, D
dc.contributor.authorKowalczyk-Quintas, C
dc.contributor.authorSchuepbach-Mallepell, S
dc.contributor.authorSmulski, CR
dc.contributor.authorEslami, M
dc.contributor.authorRolink, A
dc.contributor.authorHummler, E
dc.contributor.authorSamy, E
dc.contributor.authorNanfack, YF
dc.contributor.authorMackay, F
dc.contributor.authorLiao, M
dc.contributor.authorHess, H
dc.contributor.authorJiang, X
dc.contributor.authorSchneider, P
dc.date.accessioned2020-12-17T03:10:28Z
dc.date.available2020-12-17T03:10:28Z
dc.date.issued2018-03-23
dc.identifierpii: 10.1038/s41467-018-03323-8
dc.identifier.citationVigolo, 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., Nanfack, Y. F., Mackay, F., Liao, M., Hess, H. ,... Schneider, P. (2018). A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors. NATURE COMMUNICATIONS, 9 (1), https://doi.org/10.1038/s41467-018-03323-8.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/254775
dc.description.abstractThe 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.
dc.languageEnglish
dc.publisherNATURE PUBLISHING GROUP
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleA loop region of BAFF controls B cell survival and regulates recognition by different inhibitors
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-018-03323-8
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titleNature Communications
melbourne.source.volume9
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1320275
melbourne.contributor.authorMackay, Fabienne
dc.identifier.eissn2041-1723
melbourne.accessrightsOpen Access


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