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  • Bartsch, Yannic CUniversity of Lübeck (author)

IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • Elsevier BV,2020
  • 15 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:9c809205-b0e9-4eb0-8574-5d5e4372eff9
  • https://lup.lub.lu.se/record/9c809205-b0e9-4eb0-8574-5d5e4372eff9URI
  • https://doi.org/10.1016/j.jaci.2020.04.059DOI

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  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • BACKGROUND: Effector functions of IgG antibodies (Abs) are regulated by their Fc N-glycosylation pattern. IgG Fc glycans that lack galactose and terminal sialic acid residues correlate with the severity of inflammatory (auto)immune disorders and have also been linked to the protection against viral infection and discussed in the context of vaccine-induced protection. In contrast, sialylated IgG Abs have shown immunosuppressive effects.OBJECTIVE: We sought to investigate IgG glycosylation programming during the germinal center (GC) reaction upon immunization of mice with a foreign protein antigen and different adjuvants.METHODS: Mice were analyzed for GC T, B cell and plasma cell responses as well as antigen-specific serum IgG subclass titers and Fc glycosylation patterns.RESULTS: Different adjuvants induce distinct IgG+ GC B cell responses with specific transcriptomes and expression levels of the α2,6-sialyltransferase responsible for IgG sialylation that correspond to distinct serum IgG Fc glycosylation patterns. Low IgG Fc sialylation programming in GC B cells was overall highly dependent on the T follicular helper (TFH) cell-inducing cytokine IL-6, especially induced by water-in-oil adjuvants and Mycobacterium tuberculosis (Mtb). Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27R-dependent IFNγ+ TFH1 cells, IL-6/IL-23-dependent IL-17A+ TFH17 cells and high TFH/T follicular regulatory (TFR) cell ratios. The two latter were here dependent on Mtb and its cord factor.CONCLUSION: These findings on adjuvant-dependent GC responses and IgG glycosylation programming may aid the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns.

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  • Eschweiler, SimonUniversity of Lübeck (author)
  • Leliavski, AlexeiUniversity of Lübeck (author)
  • Lunding, Hanna BUniversity of Lübeck (author)
  • Wagt, SanderUniversity of Lübeck,Leiden University Medical Centre (author)
  • Petry, JaninaUniversity of Lübeck (author)
  • Lilienthal, Gina-MariaUniversity of Lübeck (author)
  • Rahmöller, JohannUniversity of Lübeck,University Medical Center Schleswig-Holstein (author)
  • de Haan, NoortjeLeiden University Medical Centre (author)
  • Hölscher, AlexandraResearch Center Borstel (author)
  • Erapaneedi, RaghuUniversity Hospital of Wϋrzburg (author)
  • Giannou, Anastasios DUniversity Medical Center Hamburg-Eppendorf (author)
  • Aly, LilianTechnical University of Munich (author)
  • Sato, RyotaRIKEN Center for Integrative Medical Sciences (author)
  • de Neef, Louise ALeiden University Medical Centre (author)
  • Winkler, AndréUniversity of Lübeck (author)
  • Braumann, DominiqueUniversity of Lübeck (author)
  • Hobusch, JulianeUniversity of Lübeck (author)
  • Kuhnigk, KyraUniversity of Lübeck (author)
  • Krémer, VanessaUniversity of Lübeck (author)
  • Steinhaus, MoritzUniversity of Lübeck (author)
  • Blanchard, VéroniqueCharité - University Medicine Berlin (author)
  • Gemoll, TimoUniversity of Lübeck (author)
  • Habermann, Jens KUniversity of Lübeck (author)
  • Collin, MattiasLund University,Lunds universitet,Infektionsmedicin,Sektion III,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Infektion och immunmodulering,Forskargrupper vid Lunds universitet,Infection Medicine (BMC),Section III,Department of Clinical Sciences, Lund,Faculty of Medicine,Infection and immunomodulation,Lund University Research Groups(Swepub:lu)medk-mco (author)
  • Salinas, GabrielaUniversity Medical Center Göttingen (author)
  • Manz, Rudolf AUniversity of Lübeck (author)
  • Fukuyama, HidehiroRIKEN Center for Integrative Medical Sciences (author)
  • Korn, ThomasTechnical University of Munich (author)
  • Waisman, AriJohannes-Gutenberg University Mainz (author)
  • Yogev, NirUniversity Hospital of Cologne (author)
  • Huber, SamuelUniversity Medical Center Hamburg-Eppendorf (author)
  • Rabe, BjörnUniversity of Kiel (author)
  • Rose-John, StefanUniversity of Kiel (author)
  • Busch, HaukeUniversity of Lübeck (author)
  • Berberich-Siebelt, FriederikeJulius Maximilian University of Würzburg (author)
  • Hölscher, ChristophResearch Center Borstel (author)
  • Wuhrer, ManfredLeiden University (author)
  • Ehlers, MarcUniversity of Lübeck,German Center for Lung Research (DZL),German Research Centre for Rheumatology, Berlin (author)
  • University of LübeckLeiden University Medical Centre (creator_code:org_t)

Related titles

  • In:The Journal of Allergy and Clinical Immunology: Elsevier BV146:3, s. 652-6661097-68250091-6749

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