BAFF- and TACI-Dependent Processing of BAFFR by ADAM Proteases Regulates the Survival of B Cells.

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Serval ID
serval:BIB_1C83052CD3BC
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
BAFF- and TACI-Dependent Processing of BAFFR by ADAM Proteases Regulates the Survival of B Cells.
Journal
Cell reports
Author(s)
Smulski C.R., Kury P., Seidel L.M., Staiger H.S., Edinger A.K., Willen L., Seidl M., Hess H., Salzer U., Rolink A.G., Rizzi M., Schneider P., Eibel H.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
28/02/2017
Peer-reviewed
Oui
Volume
18
Number
9
Pages
2189-2202
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
B cell activating factor (BAFF) provides B cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by B cell subsets. BAFFR is early expressed in circulating B cells and provides key signals for further maturation. Here, we report that highly regulated BAFFR processing events modulate BAFF responses. BAFFR processing is triggered by BAFF binding in B cells co-expressing TACI and it is executed by the metalloproteases ADAM10 and ADAM17. The degree of BAFF oligomerization, the expression of ADAM proteins in different B cell subsets, and the activation status of the cell determine the proteases involved in BAFFR processing. Inhibition of ADAM10 augments BAFF-dependent survival of primary human B cells, whereas inhibition of ADAM17 increases BAFFR expression levels on germinal center B cells. Therefore, BAFF-induced processing of BAFFR regulates BAFF-mediated B cell responses in a TACI-dependent manner.

Keywords
ADAM Proteins/metabolism, B-Cell Activating Factor/metabolism, B-Cell Activation Factor Receptor/metabolism, B-Lymphocyte Subsets/metabolism, Cell Line, Cell Survival/physiology, Humans, Peptide Hydrolases/metabolism, Protein Binding/physiology, Transmembrane Activator and CAML Interactor Protein/metabolism, ADAM10, ADAM17, B cell, BAFF-receptor, BAFFR, TACI, ectodomain shedding, germinal center, metalloprotease, processing, survival
Pubmed
Web of science
Open Access
Yes
Create date
07/03/2017 18:31
Last modification date
20/08/2019 12:53
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