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

Michele Vigolo, Melissa G. Chambers, Laure Willen, Dehlia Chevalley, Klaus Maskos, Alfred Lammens, Aubry Tardivel, Dolon Das, Christine Kowalczyk-Quintas, Sonia Schuepbach-Mallepell, Cristian R. Smulski, Mahya Eslami, Antonius Rolink, Edith Hummler, Eileen Samy, Yves Fomekong Nanfack, Fabienne Mackay, Maofu Liao, Henry Hess, Xuliang Jiang and Pascal Schneider ()
Additional contact information
Michele Vigolo: University of Lausanne
Melissa G. Chambers: Harvard Medical School
Laure Willen: University of Lausanne
Dehlia Chevalley: University of Lausanne
Klaus Maskos: Proteros Biostructures GmbH
Alfred Lammens: Proteros Biostructures GmbH
Aubry Tardivel: University of Lausanne
Dolon Das: University of Lausanne
Christine Kowalczyk-Quintas: University of Lausanne
Sonia Schuepbach-Mallepell: University of Lausanne
Cristian R. Smulski: University of Lausanne
Mahya Eslami: University of Lausanne
Antonius Rolink: University of Basel
Edith Hummler: University of Lausanne
Eileen Samy: EMD Serono Research & Development Institute
Yves Fomekong Nanfack: EMD Serono Research & Development Institute
Fabienne Mackay: Monash University
Maofu Liao: Harvard Medical School
Henry Hess: Merck KGaA
Xuliang Jiang: EMD Serono Research & Development Institute
Pascal Schneider: University of Lausanne

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: Abstract 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.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-03323-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03323-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-03323-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().