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

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; Mattias Collin; 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

doi:10.1016/j.jaci.2020.04.059

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

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 KrémerMoritz Steinhaus, Véronique Blanchard, Timo Gemoll, Jens K Habermann, Mattias Collin, 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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	652-666
Number of pages	15
Journal	The Journal of Allergy and Clinical Immunology
Volume	146
Issue number	3
Early online date	2020 May 20
DOIs	https://doi.org/10.1016/j.jaci.2020.04.059
Publication status	Published - 2020 Sept 1

Subject classification (UKÄ)

Immunology in the medical area
Infectious Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaci.2020.04.059Licence: CC BY-NC-ND

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Bartsch, Y. C., Eschweiler, S., Leliavski, A., Lunding, H. B., Wagt, S., Petry, J., Lilienthal, G.-M., Rahmöller, J., de Haan, N., Hölscher, A., Erapaneedi, R., Giannou, A. D., Aly, L., Sato, R., de Neef, L. A., Winkler, A., Braumann, D., Hobusch, J., Kuhnigk, K., ... Ehlers, M. (2020). IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants. The Journal of Allergy and Clinical Immunology, 146(3), 652-666. https://doi.org/10.1016/j.jaci.2020.04.059

@article{9c809205b0e94eb085745d5e4372eff9,

title = "IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants",

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.",

author = "Bartsch, {Yannic C} and Simon Eschweiler and Alexei Leliavski and Lunding, {Hanna B} and Sander Wagt and Janina Petry and Gina-Maria Lilienthal and Johann Rahm{\"o}ller and {de Haan}, Noortje and Alexandra H{\"o}lscher and Raghu Erapaneedi and Giannou, {Anastasios D} and Lilian Aly and Ryota Sato and {de Neef}, {Louise A} and Andr{\'e} Winkler and Dominique Braumann and Juliane Hobusch and Kyra Kuhnigk and Vanessa Kr{\'e}mer and Moritz Steinhaus and V{\'e}ronique Blanchard and Timo Gemoll and Habermann, {Jens K} and Mattias Collin and Gabriela Salinas and Manz, {Rudolf A} and Hidehiro Fukuyama and Thomas Korn and Ari Waisman and Nir Yogev and Samuel Huber and Bj{\"o}rn Rabe and Stefan Rose-John and Hauke Busch and Friederike Berberich-Siebelt and Christoph H{\"o}lscher and Manfred Wuhrer and Marc Ehlers",

year = "2020",

month = sep,

day = "1",

doi = "10.1016/j.jaci.2020.04.059",

language = "English",

volume = "146",

pages = "652--666",

journal = "The Journal of Allergy and Clinical Immunology",

issn = "1097-6825",

publisher = "Elsevier",

number = "3",

}

Bartsch, YC, Eschweiler, S, Leliavski, A, Lunding, HB, Wagt, S, Petry, J, Lilienthal, G-M, Rahmöller, J, de Haan, N, Hölscher, A, Erapaneedi, R, Giannou, AD, Aly, L, Sato, R, de Neef, LA, Winkler, A, Braumann, D, Hobusch, J, Kuhnigk, K, Krémer, V, Steinhaus, M, Blanchard, V, Gemoll, T, Habermann, JK, Collin, M, Salinas, G, Manz, RA, Fukuyama, H, Korn, T, Waisman, A, Yogev, N, Huber, S, Rabe, B, Rose-John, S, Busch, H, Berberich-Siebelt, F, Hölscher, C, Wuhrer, M & Ehlers, M 2020, 'IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants', The Journal of Allergy and Clinical Immunology, vol. 146, no. 3, pp. 652-666. https://doi.org/10.1016/j.jaci.2020.04.059

TY - JOUR

T1 - IgG Fc sialylation is regulated during the germinal center reaction upon 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 - Rabe, Björn

AU - Rose-John, Stefan

AU - Busch, Hauke

AU - Berberich-Siebelt, Friederike

AU - Hölscher, Christoph

AU - Wuhrer, Manfred

AU - Ehlers, Marc

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.jaci.2020.04.059

DO - 10.1016/j.jaci.2020.04.059

M3 - Article

C2 - 32445838

SN - 1097-6825

VL - 146

SP - 652

EP - 666

JO - The Journal of Allergy and Clinical Immunology

JF - The Journal of Allergy and Clinical Immunology

IS - 3

ER -

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

Abstract

Subject classification (UKÄ)

UN SDGs

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