> Detailanzeige

Kissel, Theresa; Ge, Changrong; Hafkenscheid, Lise; Kwekkeboom, Joanneke C.; Slot, Linda M.; Cavallari, Marco; He, Yibo; van Schie, Karin A.; Vergroesen, Rochelle D.; Kampstra, Arieke S.B.; Reijm, Sanne; Stoeken-Rijsbergen, Gerrie; Koeleman, Carolien; Voortman, Lennard M.; Heitman, Laura H.; Xu, Bingze; Pruijn, Ger J.M.; Wuhrer, Manfred; Rispens, Theo; Huizinga, Tom W.J.; Scherer, Hans Ulrich; Reth, Michael; Holmdahl, Rikard; Toes, Rene E.M.

Surface Ig variable domain glycosylation affects autoantigen binding and acts as threshold for human autoreactive B cell activation

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Surface Ig variable domain glycosylation affects autoantigen binding and acts as threshold for human autoreactive B cell activation
  • Beteiligte: Kissel, Theresa; Ge, Changrong; Hafkenscheid, Lise; Kwekkeboom, Joanneke C.; Slot, Linda M.; Cavallari, Marco; He, Yibo; van Schie, Karin A.; Vergroesen, Rochelle D.; Kampstra, Arieke S.B.; Reijm, Sanne; Stoeken-Rijsbergen, Gerrie; Koeleman, Carolien; Voortman, Lennard M.; Heitman, Laura H.; Xu, Bingze; Pruijn, Ger J.M.; Wuhrer, Manfred; Rispens, Theo; Huizinga, Tom W.J.; Scherer, Hans Ulrich; Reth, Michael; Holmdahl, Rikard; Toes, Rene E.M.
  • Erschienen: American Association for the Advancement of Science (AAAS), 2022
  • Erschienen in: Science Advances, 8 (2022) 6
  • Sprache: Englisch
  • DOI: 10.1126/sciadv.abm1759
  • ISSN: 2375-2548
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: The hallmark autoantibodies in rheumatoid arthritis are characterized by variable domain glycans (VDGs). Their abundant occurrence results from the selective introduction of N-linked glycosylation sites during somatic hypermutation, and their presence is predictive for disease development. However, the functional consequences of VDGs on autoreactive B cells remain elusive. Combining crystallography, glycobiology, and functional B cell assays allowed us to dissect key characteristics of VDGs on human B cell biology. Crystal structures showed that VDGs are positioned in the vicinity of the antigen-binding pocket, and dynamic modeling combined with binding assays elucidated their impact on binding. We found that VDG-expressing B cell receptors stay longer on the B cell surface and that VDGs enhance B cell activation. These results provide a rationale on how the acquisition of VDGs might contribute to the breach of tolerance of autoreactive B cells in a major human autoimmune disease.
  • Zugangsstatus: Freier Zugang