A loop region of BAFF controls B cell survival and regulates recognition by different inhibitors
AuthorVigolo, M; Chambers, MG; Willen, L; Chevalley, D; Maskos, K; Lammens, A; Tardivel, A; Das, D; Kowalczyk-Quintas, C; Schuepbach-Mallepell, S; ...
Source TitleNature Communications
PublisherNATURE PUBLISHING GROUP
University of Melbourne Author/sMackay, Fabienne
AffiliationMicrobiology and Immunology
Document TypeJournal Article
CitationsVigolo, 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.
Access StatusOpen Access
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.
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References