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

Publication date: 28 February 2017
Source:Cell Reports, Volume 18, Issue 9
Author(s): 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
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.

Graphical abstract

Teaser

Smulski et al. report that the B cell survival receptor BAFFR undergoes ligand-induced shedding but only in cells co-expressing a second receptor for BAFF called TACI. BAFFR shedding can be performed by ADAM10 in circulating B cells or by ADAM17 in germinal center B cells and limits BAFF-mediated survival signals.


from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2lQXoH5
via IFTTT