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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:146

Article

Bartsch, Yannic C.^1,2  Eschweiler, Simon^1,2  Leliavski, Alexei^1,2  Lunding, Hanna B.^1,2  Wagt, Sander^1,2  Petry, Janina^1,2  Lilienthal, Gina-Maria^1,2  Rahmoller, Johann^1,2,4  de Haan, Noortje³  Holscher, Alexandra⁵  Erapaneedi, Raghu⁶  Giannou, Anastasios D.⁷  Aly, Lilian⁸  Sato, Ryota⁹  de Neef, Louise A.³  Winkler, Andre^1,2,10,15  Braumann, Dominique^{1,2,11,12,13,15}  Hobusch, Juliane^1,2  Kuhnigk, Kyra^1,2  Kremer, Vanessa^1,2  Steinhaus, Moritz^1,2  Blanchard, Veronique^11,12,13  Gemoll, Timo^14,15  Habermann, Jens K.^14,15  Collin, Mattias¹⁶  Salinas, Gabriela¹⁷  Manz, Rudolf A.¹⁸  Fukuyama, Hidehiro⁹  Korn, Thomas¹⁹  Waisman, Ari²⁰  Yogev, Nir²¹  Huber, Samuel⁷  Rabe, Bjorn²²  Rose-John, Stefan²²  Busch, Hauke²³  Berberich-Siebelt, Friederike^6,24  Holscher, Christoph^5,25  Wuhrer, Manfred³  Ehlers, Marc^1,2,26 

[1] Univ Lubeck, Inst Nutr Med, Labs Immunol & Antibody Glycan Anal, Lubeck, Germany

[2] Univ Med Ctr Schleswig Holstein, Lubeck, Germany

[3] Leiden Univ, Med Ctr, Ctr Prote & Metabol, Leiden, Germany

[4] Univ Med Ctr Schleswig Holstein, Dept Anesthesiol & Intens Care, Kiel, Germany

[5] Res Ctr Borstel, Infect Immunol, Borstel, Germany

[6] Univ Wurzburg, Inst Pathol, Wurzburg, Germany

[7] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany

[8] Tech Univ Munich, Klinikum Rechts Isar, Dept Neurol, Munich, Germany

[9] RIKEN Ctr Integrat Med Sci, Lab Lymphocyte Differentiat, Yokohama, Kanagawa, Japan

[10] Leibniz Inst, German Rheumatism Res Ctr, Lab Tolerance & Autoimmun, Berlin, Germany

[11] Charite Univ Med Berlin, Inst Lab Med Clin Chem & Pathobiochem, Berlin, Germany

[12] Free Univ Berlin, Humboldt Univ Berlin, Berlin, Germany

[13] Berlin Inst Hlth, Berlin, Germany

[14] Univ Lubeck, Dept Surg, Sect Translat Surg Oncol & Biobanking, Lubeck, Germany

[15] Univ Med Ctr Schleswig Holstein, Kiel, Germany

[16] Lund Univ, Dept Clin Sci, Div Infect Med, Lund, Sweden

[17] Univ Med Ctr Gottingen, Inst Human Genet, NGS Integrat Genom, Gottingen, Germany

[18] Univ Lubeck, Inst Syst Inflammat Res, Lubeck, Germany

[19] SyNergy, Munich Cluster Syst Neurol, Munich, Germany

[20] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, Mainz, Germany

[21] Univ Hosp Cologne, Clin & Polyclin Dermatol & Venerol, Cologne, Germany

[22] Univ Kiel, Inst Biochem, Kiel, Germany

[23] Univ Lubeck, Lubeck Inst Expt Dermatol, Lubeck, Germany

[24] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, Wurzburg, Germany

[25] Partner Site Hamburg Lubeck Borstel Riems, German Ctr Infect Res, Hamburg, Germany

[26] Univ Lubeck, Airway Res Ctr North, Lubeck, Germany

关键词: Antibodies;    IgG glycosylation;    vaccination;    adjuvants;    germinal center;    T follicular cells;    IL-6;    IL-27R;    IL-17;    IFN-gamma;   

DOI  :  10.1016/j.jaci.2020.04.059

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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