A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans
Hagelkruys A, Wirnsberger G, Stadlmann J, Wöhner M, Horrer M, Vilagos B, Jonsson G, Kogler M, Tortola L, Novatchkova M, Bönelt P, Hoffmann D, Koglgruber R, Steffen U, Schett G, Busslinger M, Bergthaler A, Klein C, Penninger JM (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 218
Article Number: e20200559
Journal Issue: 1
DOI: 10.1084/JEM.20200559
Abstract
Jagunal homolog 1 (JAGN1) has been identified as a critical regulator of neutrophil biology in mutant mice and rare-disease patients carrying JAGN1 mutations. Here, we report that Jagn1 deficiency results in alterations in the endoplasmic reticulum (ER) of antibody-producing cells as well as decreased antibody production and secretion. Consequently, mice lacking Jagn1 in B cells exhibit reduced serum immunoglobulin (Ig) levels at steady state and fail to mount an efficient humoral immune response upon immunization with specific antigens or when challenged with viral infections. We also demonstrate that Jagn1 deficiency in B cells results in aberrant IgG N-glycosylation leading to enhanced Fc receptor binding. Jagn1 deficiency in particular affects fucosylation of IgG subtypes in mice as well as rare-disease patients with loss-of-function mutations in JAGN1. Moreover, we show that ER stress affects antibody glycosylation. Our data uncover a novel and key role for JAGN1 and ER stress in antibody glycosylation and humoral immunity in mice and humans.
Authors with CRIS profile
Miriam Wöhner
Ulrike Steffen Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III
Ulrike Steffen Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III
Involved external institutions
Institut für Molekulare Biotechnologie / Institute of Molecular Biotechnology (IMBA)
Austria (AT)
Österreichische Akademie der Wissenschaften
Austria (AT)
Forschungsinstitut für Molekulare Pathologie / Research Institute of Molecular Pathology (IMP)
Austria (AT)
Klinikum der Universität München
Germany (DE)
Austria (AT)
Österreichische Akademie der Wissenschaften
Austria (AT)
Forschungsinstitut für Molekulare Pathologie / Research Institute of Molecular Pathology (IMP)
Austria (AT)
Klinikum der Universität München
Germany (DE)
How to cite
APA:
Hagelkruys, A., Wirnsberger, G., Stadlmann, J., Wöhner, M., Horrer, M., Vilagos, B.,... Penninger, J.M. (2020). A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans. Journal of Experimental Medicine, 218(1). https://doi.org/10.1084/JEM.20200559
MLA:
Hagelkruys, Astrid, et al. "A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans." Journal of Experimental Medicine 218.1 (2020).
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