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

Cristian R. SmulskiPatrick KuryLea M. SeidelHannah S. StaigerAnna K. EdingerLaure WillenMaximilian SeidlHenry HessUlrich SalzerAntonius G. RolinkMarta RizziPascal SchneiderHermann Eibel

出版	Universität, 2017
URL	http://books.google.com.hk/books?id=jkORzgEACAAJ&hl=&source=gbs_api

註釋Abstract: B cell activating factor (BAFF) provides B cells withessential survival signals. It binds to three receptors:BAFFR, TACI, and BCMA that are differentially ex-pressed by B cell subsets. BAFFR is early expressedin circulating B cells and provides key signals forfurther maturation. Here, we report that highly regu-lated BAFFR processing events modulate BAFFresponses. BAFFR processing is triggered by BAFFbinding in B cells co-expressing TACI and it isexecuted by the metalloproteases ADAM10 andADAM17. The degree of BAFF oligomerization, theexpression of ADAM proteins in different B cell sub-sets, and the activation status of the cell determinethe proteases involved in BAFFR processing. Inhibi-tion of ADAM10 augments BAFF-dependent sur-vival of primary human B cells, whereas inhibitionof ADAM17 increases BAFFR expression levels ongerminal center B cells. Therefore, BAFF-inducedprocessing of BAFFR regulates BAFF-mediated Bcell responses in a TACI-dependent manner