دورية أكاديمية
أعرض في EDS

A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans.

التفاصيل البيبلوغرافية
العنوان: A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans.
المؤلفون: Hagelkruys A; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Wirnsberger G; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.; Apeiron Biologics AG, Vienna, Austria., Stadlmann J; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.; Institute of Biochemistry, University of Natural Resource and Life Sciences, Vienna, Austria., Wöhner M; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria., Horrer M; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Vilagos B; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Jonsson G; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Kogler M; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Tortola L; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.; Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland., Novatchkova M; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria., Bönelt P; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria., Hoffmann D; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Koglgruber R; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria., Steffen U; Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany., Schett G; Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany., Busslinger M; Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria., Bergthaler A; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria., Klein C; Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich, Germany., Penninger JM; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.; Department of Medical Genetics, Life Science Institute, University of British Columbia, Vancouver, Canada.
المصدر: The Journal of experimental medicine [J Exp Med] 2021 Jan 04; Vol. 218 (1).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Rockefeller University Press Country of Publication: United States NLM ID: 2985109R Publication Model: Print Cited Medium: Internet ISSN: 1540-9538 (Electronic) Linking ISSN: 00221007 NLM ISO Abbreviation: J Exp Med Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Rockefeller University Press
مواضيع طبية MeSH: Immunity, Humoral*, Endoplasmic Reticulum Stress/*immunology , Immunoglobulin G/*immunology , Membrane Proteins/*immunology, Animals ; Endoplasmic Reticulum Stress/genetics ; Glycosylation ; Humans ; Immunoglobulin G/genetics ; Loss of Function Mutation ; Membrane Proteins/genetics ; Mice, Knockout ; Receptors, Fc/genetics ; Receptors, Fc/immunology ; Mice
مستخلص: 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.
Competing Interests: Disclosures: The authors declare no competing interests exist.
(© 2020 Hagelkruys et al.)
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معلومات مُعتمدة: Z 271 Austria FWF_ Austrian Science Fund FWF
المشرفين على المادة: 0 (Immunoglobulin G)
0 (JAGN1 protein, human)
0 (Membrane Proteins)
0 (Receptors, Fc)
تواريخ الأحداث: Date Created: 20200915 Date Completed: 20210830 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC7953624
DOI: 10.1084/jem.20200559
PMID: 32930709
قاعدة البيانات: MEDLINE
الوصف
تدمد:1540-9538
DOI:10.1084/jem.20200559