IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants
(2020) In The Journal of Allergy and Clinical Immunology 146(3). p.652-666- 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... (More)
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.
(Less)
- author
- 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
LU
; Salinas, Gabriela
; Manz, Rudolf A
; Fukuyama, Hidehiro
; Korn, Thomas
; Waisman, Ari
; Yogev, Nir
; Huber, Samuel
; Rabe, Björn
; Rose-John, Stefan
; Busch, Hauke
; Berberich-Siebelt, Friederike
; Hölscher, Christoph
; Wuhrer, Manfred
and Ehlers, Marc
(Less) - organization
- publishing date
- 2020-09-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- The Journal of Allergy and Clinical Immunology
- volume
- 146
- issue
- 3
- pages
- 15 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:85087782292
- pmid:32445838
- ISSN
- 1097-6825
- DOI
- 10.1016/j.jaci.2020.04.059
- language
- English
- LU publication?
- yes
- id
- 9c809205-b0e9-4eb0-8574-5d5e4372eff9
- date added to LUP
- 2020-05-29 10:10:34
- date last changed
- 2024-06-27 18:23:03
@article{9c809205-b0e9-4eb0-8574-5d5e4372eff9,
abstract = {{<p>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.</p><p>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.</p><p>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.</p><p>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.</p><p>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.</p>}},
author = {{Bartsch, Yannic C and Eschweiler, Simon and Leliavski, Alexei and Lunding, Hanna B and Wagt, Sander and Petry, Janina and Lilienthal, Gina-Maria and Rahmöller, Johann and de Haan, Noortje and Hölscher, Alexandra and Erapaneedi, Raghu and Giannou, Anastasios D and Aly, Lilian and Sato, Ryota and de Neef, Louise A and Winkler, André and Braumann, Dominique and Hobusch, Juliane and Kuhnigk, Kyra and Krémer, Vanessa and Steinhaus, Moritz and Blanchard, Véronique and Gemoll, Timo and Habermann, Jens K and Collin, Mattias and Salinas, Gabriela and Manz, Rudolf A and Fukuyama, Hidehiro and Korn, Thomas and Waisman, Ari and Yogev, Nir and Huber, Samuel and Rabe, Björn and Rose-John, Stefan and Busch, Hauke and Berberich-Siebelt, Friederike and Hölscher, Christoph and Wuhrer, Manfred and Ehlers, Marc}},
issn = {{1097-6825}},
language = {{eng}},
month = {{09}},
number = {{3}},
pages = {{652--666}},
publisher = {{Elsevier}},
series = {{The Journal of Allergy and Clinical Immunology}},
title = {{IgG Fc sialylation is regulated during the germinal center reaction upon immunization with different adjuvants}},
url = {{http://dx.doi.org/10.1016/j.jaci.2020.04.059}},
doi = {{10.1016/j.jaci.2020.04.059}},
volume = {{146}},
year = {{2020}},
}