De novo ceramide synthesis is required for n-linked glycosylation in plasma cells

Meidan Goldfinger, Elad L. Laviad, Rivka Hadar, Miri Shmuel, Arie Dagan, Hyejung Park, Alfred H. Merrill, Israel Ringel, Anthony H. Futerman, Boaz Tirosh*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Plasma cells (PCs) are terminally differentiated B lymphocytes responsible for the synthesis and secretion of Igs. The differentiation of B cells into PCs involves a remarkable expansion of both lipid and protein components of the endoplasmic reticulum. Despite their importance in many signal transduction pathways, the role of ceramides, and of complex sphingolipids that are derived from ceramide, in PC differentiation has never been directly studied. To assess their putative role in PC differentiation, we blocked ceramide synthesis with fumonisin B1, a specific inhibitor of ceramide synthase. Under fumonisin B1 treatment, N-linked glycosylation was severely impaired in LPS-activated, but not in naive, B cells. We also show that ceramide synthesis is strongly induced by XBP-1 (X box-binding protein-1). In the absence of ceramide synthesis, ER expansion was dramatically diminished. Our results underscore ceramide biosynthesis as a key metabolic pathway in the process of PC differentiation and reveal a previously unknown functional link between sphingolipids and N-linked glycosylation in PCs.

Original languageAmerican English
Pages (from-to)7038-7047
Number of pages10
JournalJournal of Immunology
Volume182
Issue number11
DOIs
StatePublished - 1 Jun 2009

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