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

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
Organisations
External organisations
  • University of Lübeck
  • Leiden University Medical Centre
  • University Medical Center Schleswig-Holstein Campus Lubeck
  • Research Center Borstel
  • Wurzburg University Medical Center
  • University Medical Center Hamburg-Eppendorf
  • Technical University of Munich
  • RIKEN Center for Integrative Medical Sciences
  • Charité - University Medicine 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)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
  • Infectious Medicine
Original languageEnglish
JournalThe Journal of Allergy and Clinical Immunology
Publication statusE-pub ahead of print - 2020 May 20
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

Copyright © 2020. Published by Elsevier Inc.