Bartsch, Yannic C., Eschweiler, Simon ORCID: 0000-0002-6379-8588, Leliavski, Alexei, Lunding, Hanna B., Wagt, Sander, Petry, Janina, Lilienthal, Gina-Maria, Rahmoller, Johann, de Haan, Noortje, Holscher, Alexandra, Erapaneedi, Raghu, Giannou, Anastasios D., Aly, Lilian, Sato, Ryota, de Neef, Louise A., Winkler, Andre, Braumann, Dominique, Hobusch, Juliane, Kuhnigk, Kyra, Kremer, Vanessa, Steinhaus, Moritz, Blanchard, Veronique, Gemoll, Timo, Habermann, Jens K., Collin, Mattias ORCID: 0000-0002-6166-7410, Salinas, Gabriela, Manz, Rudolf A., Fukuyama, Hidehiro ORCID: 0000-0002-6457-0630, Korn, Thomas, Waisman, Ari, Yogev, Nir, Huber, Samuel, Rabe, Bjorn, Rose-John, Stefan, Busch, Hauke ORCID: 0000-0003-4763-4521, Berberich-Siebelt, Friederike, Holscher, Christoph, Wuhrer, Manfred ORCID: 0000-0002-0814-4995 and Ehlers, Marc ORCID: 0000-0002-5383-8603 (2020). IgG Fc sialylation is regulated during the germinal center reaction following immunization with different adjuvants. J. Allergy Clin. Immunol., 146 (3). S. 652 - 678. NEW YORK: MOSBY-ELSEVIER. ISSN 1097-6825

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Abstract

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 alpha 2,6-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-inoil adjuvants and Mycobacterium tuberculosis. Furthermore, low IgG Fc sialylation programming was dependent on adjuvants that induced IL-27 receptor-dependent IFN-gamma(+) TFH1 cells, IL-6/IL-23-dependent IL-17A(+) T-FH17 cells, and high ratios of TFH cells to Foxp31 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Bartsch, Yannic C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eschweiler, SimonUNSPECIFIEDorcid.org/0000-0002-6379-8588UNSPECIFIED
Leliavski, AlexeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lunding, Hanna B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagt, SanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petry, JaninaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lilienthal, Gina-MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rahmoller, JohannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Haan, NoortjeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holscher, AlexandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erapaneedi, RaghuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giannou, Anastasios D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aly, LilianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sato, RyotaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Neef, Louise A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winkler, AndreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Braumann, DominiqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hobusch, JulianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kuhnigk, KyraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kremer, VanessaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinhaus, MoritzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blanchard, VeroniqueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gemoll, TimoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Habermann, Jens K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Collin, MattiasUNSPECIFIEDorcid.org/0000-0002-6166-7410UNSPECIFIED
Salinas, GabrielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Manz, Rudolf A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fukuyama, HidehiroUNSPECIFIEDorcid.org/0000-0002-6457-0630UNSPECIFIED
Korn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Waisman, AriUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yogev, NirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, SamuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rabe, BjornUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rose-John, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Busch, HaukeUNSPECIFIEDorcid.org/0000-0003-4763-4521UNSPECIFIED
Berberich-Siebelt, FriederikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Holscher, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wuhrer, ManfredUNSPECIFIEDorcid.org/0000-0002-0814-4995UNSPECIFIED
Ehlers, MarcUNSPECIFIEDorcid.org/0000-0002-5383-8603UNSPECIFIED
URN: urn:nbn:de:hbz:38-321525
DOI: 10.1016/j.jaci.2020.04.059
Journal or Publication Title: J. Allergy Clin. Immunol.
Volume: 146
Number: 3
Page Range: S. 652 - 678
Date: 2020
Publisher: MOSBY-ELSEVIER
Place of Publication: NEW YORK
ISSN: 1097-6825
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IFN-GAMMA RECEPTOR; HELPER T-CELLS; ANTIINFLAMMATORY ACTIVITY; ANTIBODY GLYCOSYLATION; PLASMA-CELL; B-CELLS; INFLAMMATION; RESPONSES; IMMUNE; SIGNATURESMultiple languages
Allergy; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/32152

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