IgG Fc sialylation is regulated during the germinal center reaction following immunization with different adjuvants
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IgG Fc sialylation is regulated during the germinal center reaction following immunization with different adjuvants. / Bartsch, Yannic C; Eschweiler, Simon; Leliavski, Alexei; Lunding, Hanna B; Wagt, Sander; Petry, Janina; Lilienthal, Gina-Maria; Rahmöller, Johann; de Haan, Noortje; Hölscher, Alexandra; Erapaneedi, Raghu; Giannou, Anastasios D; Aly, Lilian; Sato, Ryota; de Neef, Louise A; Winkler, André; Braumann, Dominique; Hobusch, Juliane; Kuhnigk, Kyra; Krémer, Vanessa; Steinhaus, Moritz; Blanchard, Véronique; Gemoll, Timo; Habermann, Jens K; Collin, Mattias; Salinas, Gabriela; Manz, Rudolf A; Fukuyama, Hidehiro; Korn, Thomas; Waisman, Ari; Yogev, Nir; Huber, Samuel; Germany, Institute of Biochemistry Kiel University; Rose-John, Stefan; Busch, Hauke; Berberich-Siebelt, Friederike; Hölscher, Christoph; Netherlands, Center for Proteomics and Metabolomics Leiden University Medical Center Leiden; Ehlers, Marc.
in: J ALLERGY CLIN IMMUN, Jahrgang 146, Nr. 3, 09.2020, S. 652-666.e11.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - IgG Fc sialylation is regulated during the germinal center reaction following immunization with different adjuvants
AU - Bartsch, Yannic C
AU - Eschweiler, Simon
AU - Leliavski, Alexei
AU - Lunding, Hanna B
AU - Wagt, Sander
AU - Petry, Janina
AU - Lilienthal, Gina-Maria
AU - Rahmöller, Johann
AU - de Haan, Noortje
AU - Hölscher, Alexandra
AU - Erapaneedi, Raghu
AU - Giannou, Anastasios D
AU - Aly, Lilian
AU - Sato, Ryota
AU - de Neef, Louise A
AU - Winkler, André
AU - Braumann, Dominique
AU - Hobusch, Juliane
AU - Kuhnigk, Kyra
AU - Krémer, Vanessa
AU - Steinhaus, Moritz
AU - Blanchard, Véronique
AU - Gemoll, Timo
AU - Habermann, Jens K
AU - Collin, Mattias
AU - Salinas, Gabriela
AU - Manz, Rudolf A
AU - Fukuyama, Hidehiro
AU - Korn, Thomas
AU - Waisman, Ari
AU - Yogev, Nir
AU - Huber, Samuel
AU - Germany, Institute of Biochemistry Kiel University
AU - Rose-John, Stefan
AU - Busch, Hauke
AU - Berberich-Siebelt, Friederike
AU - Hölscher, Christoph
AU - Netherlands, Center for Proteomics and Metabolomics Leiden University Medical Center Leiden
AU - Ehlers, Marc
N1 - Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2020/9
Y1 - 2020/9
N2 - BACKGROUND: Effector functions of IgG 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 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 following immunization of mice with a foreign protein antigen and different adjuvants.METHODS: Mice were analyzed for GC T-cell, B-cell, and plasma cell responses, as well as for 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 Foxp3- follicular helper T (TFH) cell-inducing cytokine IL-6, here in particular induced by water-in-oil adjuvants and Mycobacterium tuberculosis. Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27 receptor-dependent IFN-γ+ TFH1 cells, IL-6/IL-23-dependent IL-17A+ TFH17 cells, and high ratios of TFH cells to Foxp3+ follicular regulatory T cells. Here, the 2 latter were dependent on M tuberculosis and its cord factor.CONCLUSION: This study's findings regarding adjuvant-dependent GC responses and IgG glycosylation programming may aid in the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns in the GC.
AB - BACKGROUND: Effector functions of IgG 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 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 following immunization of mice with a foreign protein antigen and different adjuvants.METHODS: Mice were analyzed for GC T-cell, B-cell, and plasma cell responses, as well as for 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 Foxp3- follicular helper T (TFH) cell-inducing cytokine IL-6, here in particular induced by water-in-oil adjuvants and Mycobacterium tuberculosis. Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27 receptor-dependent IFN-γ+ TFH1 cells, IL-6/IL-23-dependent IL-17A+ TFH17 cells, and high ratios of TFH cells to Foxp3+ follicular regulatory T cells. Here, the 2 latter were dependent on M tuberculosis and its cord factor.CONCLUSION: This study's findings regarding adjuvant-dependent GC responses and IgG glycosylation programming may aid in the development of novel vaccination strategies to induce IgG Abs with both high affinity and defined Fc glycosylation patterns in the GC.
U2 - 10.1016/j.jaci.2020.04.059
DO - 10.1016/j.jaci.2020.04.059
M3 - SCORING: Journal article
C2 - 32445838
VL - 146
SP - 652-666.e11
JO - J ALLERGY CLIN IMMUN
JF - J ALLERGY CLIN IMMUN
SN - 0091-6749
IS - 3
ER -