Journal
BLOOD
Volume 117, Issue 23, Pages 6162-6171Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-12-325522
Keywords
-
Categories
Funding
- Dutch Cancer Society
- Netherlands Organization for Health Research and Development
- Swedish Research Council [K2009-67X-21128-01-3]
Ask authors/readers for more resources
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. (Blood. 2011;117(23):6162-6171)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available