{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:41:48Z","timestamp":1791013308975,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,5,11]],"date-time":"2010-05-11T00:00:00Z","timestamp":1273536000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["084631"],"award-info":[{"award-number":["084631"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Glycosphingolipid storage diseases are a group of inherited metabolic diseases in which glycosphingolipids accumulate due to their impaired lysosomal breakdown. Splenic B cells isolated from NPC1, Sandhoff, GM1\u2010gangliosidosis and Fabry disease mouse models showed large (20\u2010 to 30\u2010fold) increases in disease specific glycosphingolipids and up to a 4\u2010fold increase in cholesterol. The magnitude of glycosphingolipid storage was in the order NPC1 &gt; Sandhoff \u223c GM1 gangliosidosis &gt; Fabry. Except for Fabry disease, glycosphingolipid storage led to an increase in the lysosomal compartment and altered glycosphingolipid trafficking. In order to investigate the consequences of storage on B cell function, the levels of surface expression of B cell IgM receptor and its associated components were quantitated in Sandhoff B cells, since they are all raft\u2010associated on activation. Both the B cell receptor, CD21 and CD19 had decreased cell surface expression. In contrast, CD40 and MHC II, surface receptors that do not associate with lipid rafts, were unchanged. Using a pulse chase biotinylation procedure, surface B cell receptors on a Sandhoff lymphoblast cell line were found to have a significantly decreased half\u2010life. Increased co\u2010localization of fluorescently conjugated cholera toxin and lysosomes was also observed in Sandhoff B cells. Glycosphingolipid storage leads to the enhanced formation of lysosomal lipid rafts, altered endocytic trafficking and increased degradation of the B cell receptor.<\/jats:p>","DOI":"10.1007\/s10545-010-9109-3","type":"journal-article","created":{"date-parts":[[2010,5,10]],"date-time":"2010-05-10T07:45:50Z","timestamp":1273477550000},"page":"261-270","source":"Crossref","is-referenced-by-count":15,"title":["Glycosphingolipid storage leads to the enhanced degradation of the B cell receptor in Sandhoff disease mice"],"prefix":"10.1002","volume":"33","author":[{"given":"Danielle","family":"te Vruchte","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Oxford Mansfield Road Oxford OX1 3QT UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aruna","family":"Jeans","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Oxford Mansfield Road Oxford OX1 3QT 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