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Disruption of hepar...
Disruption of heparan sulfate proteoglycan conformation perturbs B-cell maturation and APRIL-mediated plasma cell survival
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Reijmers, Rogier M. (author)
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Groen, Richard W. J. (author)
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Kuil, Annemieke (author)
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Weijer, Kees (author)
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Kimberley, Fiona C. (author)
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Medema, Jan Paul (author)
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van Kuppevelt, Toin H. (author)
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- Li, Jin-Ping (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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Spaargaren, Marcel (author)
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Pals, Steven T. (author)
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(creator_code:org_t)
- American Society of Hematology, 2011
- 2011
- English.
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In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 117:23, s. 6162-6171
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- 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.
Keyword
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Reijmers, Rogier ...
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Groen, Richard W ...
-
Kuil, Annemieke
-
Weijer, Kees
-
Kimberley, Fiona ...
-
Medema, Jan Paul
-
show more...
-
van Kuppevelt, T ...
-
Li, Jin-Ping
-
Spaargaren, Marc ...
-
Pals, Steven T.
-
show less...
- Articles in the publication
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Blood
- By the university
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Uppsala University