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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

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.

Detaljer

Författare
  • Yannic C Bartsch
  • Simon Eschweiler
  • Alexei Leliavski
  • Hanna B Lunding
  • Sander Wagt
  • Janina Petry
  • Gina-Maria Lilienthal
  • Johann Rahmöller
  • Noortje de Haan
  • Alexandra Hölscher
  • Raghu Erapaneedi
  • Anastasios D Giannou
  • Lilian Aly
  • Ryota Sato
  • Louise A de Neef
  • André Winkler
  • Dominique Braumann
  • Juliane Hobusch
  • Kyra Kuhnigk
  • Vanessa Krémer
  • Moritz Steinhaus
  • Véronique Blanchard
  • Timo Gemoll
  • Jens K Habermann
  • Gabriela Salinas
  • Rudolf A Manz
  • Hidehiro Fukuyama
  • Thomas Korn
  • Ari Waisman
  • Nir Yogev
  • Samuel Huber
  • Björn Rabe
  • Stefan Rose-John
  • Hauke Busch
  • Friederike Berberich-Siebelt
  • Christoph Hölscher
  • Manfred Wuhrer
  • Marc Ehlers
Enheter & grupper
Externa organisationer
  • University of Lübeck
  • Leiden University Medical Centre
  • University Medical Center Schleswig-Holstein Campus Lubeck
  • Research Center Borstel
  • University Hospital of Wϋrzburg
  • University Medical Center Hamburg-Eppendorf
  • Technical University of Munich
  • RIKEN Center for Integrative Medical Sciences
  • Charité Universitätsmedizin Berlin
  • University Medical Center Göttingen
  • University of Mainz
  • University Hospital of Cologne
  • University of Kiel
  • Julius Maximilian University of Würzburg
  • Leiden University
  • German Research Centre for Rheumatology, Berlin
  • German Center for Lung Research (DZL)
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Immunologi inom det medicinska området
  • Infektionsmedicin
Originalspråkengelska
Sidor (från-till)652-666
Antal sidor15
TidskriftThe Journal of Allergy and Clinical Immunology
Volym146
Utgåva nummer3
Tidigt onlinedatum2020 maj 20
StatusPublished - 2020 sep 1
PublikationskategoriForskning
Peer review utfördJa