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

• DOI: 10.1016/j.celrep.2017.02.005
• Publication Date: 2017-02-28T23:15:43Z
• Authors: Cristian R. Smulski; Patrick Kury; Lea M. Seidel; Hannah S. Staiger; Anna K. Edinger; Laure Willen; Maximilan Seidl; Henry Hess; Ulrich Salzer; Antonius G. Rolink; Marta Rizzi; Pascal Schneider; Hermann Eibel
• Keywords: 0301 basic medicine; QH301-705.5; Cell Survival; Transmembrane Activator and CAML Interactor Protein; B-Lymphocyte Subsets; 610; Cell Line; ADAM Proteins; 03 medical and health sciences; B-Cell Activating Factor; Humans; 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; Biology (General); B-Cell Activation Factor Receptor; Peptide Hydrolases; Protein Binding

B cell activating factor (BAFF) provides cells with essential survival signals. It binds to three receptors: BAFFR, TACI, and BCMA that are differentially expressed by subsets. BAFFR is early in circulating key signals for further maturation. Here, we report highly regulated processing events modulate BAFF responses. triggered binding co-expressing TACI it executed the metalloproteases ADAM10 ADAM17. The degree of oligomerization, expression ADAM proteins different subsets, activation status determine proteases involved processing. Inhibition augments BAFF-dependent primary human cells, whereas inhibition ADAM17 increases levels on germinal center cells. Therefore, BAFF-induced regulates BAFF-mediated responses a TACI-dependent manner.