Disruption of heparan sulfate proteoglycan conformation perturbs B-cell maturation and APRIL-mediated plasma cell survival

Rogier M. Reijmers, Richard W. J. Groen, Annemieke Kuil, Kees Weijer, Fiona C. Kimberley, Jan Paul Medema, Toin H. van Kuppevelt, Jin-Ping Li, Marcel Spaargaren, Steven T. Pals

Research output: Contribution to journalArticleAcademicpeer-review

43 Citations (Scopus)


The development and antigen-dependent differentiation of B lymphocytes are orchestrated by an array of growth factors, cytokines, and chemokines that require tight spatiotemporal regulation. Heparan sulfate proteoglycans specifically bind and regulate the bioavailability of soluble protein ligands, but their role in the immune system has remained largely unexplored. Modification of heparan sulfate by glucuronyl C5-epimerase (Glce) controls heparan sulfate-chain flexibility and thereby affects ligand binding. Here we show that Glce deficiency impairs B-cell maturation, resulting in decreased plasma cell numbers and immunoglobulin levels. We demonstrate that C5-epimerase modification of heparan sulfate is critical for binding of a proliferation inducing ligand (APRIL) and that Glce-deficient plasma cells fail to respond to APRIL-mediated survival signals. Our results identify heparan sulfate proteoglycans as novel players in B-cell maturation and differentiation and suggest that heparan sulfate conformation is crucial for recruitment of factors that control plasma cell survival
Original languageEnglish
Pages (from-to)6162-6171
Number of pages10
Issue number23
Publication statusPublished - 9 Jun 2011


  • Animals
  • Carbohydrate Epimerases/genetics
  • Cell Differentiation/genetics
  • Cell Survival/genetics
  • Heparan Sulfate Proteoglycans/genetics
  • Mice
  • Mice, Knockout
  • Plasma Cells/enzymology
  • Signal Transduction/genetics
  • Tumor Necrosis Factor Ligand Superfamily Member 13/genetics

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