γ-secretase directly sheds the survival receptor BCMA from plasma cells

• DOI: 10.1038/ncomms8333
• Publication Date: 2015-06-11T12:38:28Z
• Authors: Sarah A. Laurent; Franziska S. Hoff...; Peer-Hendrik Kuhn; Qingyu Cheng; Yuanyuan Chu; Marc Schmidt-Supp...; Stefanie M. Hauck; Elisabeth Schuh; Markus Krumbholz; Heike Rübsamen; Johanna Wanngren; Mohsen Khademi; Tomas Olsson; Tobias Alexander; Falk Hiepe; Hans-Walter Pfister; Frank Weber; Dieter Jenne; Hartmut Wekerle; Reinhard Hohlfeld; Stefan F. Lichten...; Edgar Meinl
• Keywords: 0301 basic medicine; Plasma Cells; Cell Differentiation; antagonists & inhibitors [Amyloid Precursor Protein Secretases]; metabolism [Plasma Cells]; metabolism [Amyloid Precursor Protein Secretases]; Article; ddc:; cytology [Plasma Cells]; 03 medical and health sciences; HEK293 Cells; Humans; ddc:500; metabolism [B-Cell Maturation Antigen]; Amyloid Precursor Protein Secretases; B-Cell Maturation Antigen; TNFRSF17 protein, human

Abstract Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation another protease. This direct shedding facilitated the short length BCMA’s extracellular domain. In vitro , reduces BCMA-mediated NF-κB activation. addition, releases soluble BCMA (sBCMA) acts as decoy neutralizing vivo inhibition enhances surface expression in increases their number bone marrow. Furthermore, multiple sclerosis, sBCMA levels spinal fluid are elevated associated with intracerebral IgG production; systemic lupus erythematosus, serum correlate disease activity. Together, controls marrow yields potential biomarker for involvement human autoimmune diseases.