A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans
| Autor: | Luigi Tortola, Rubina Koglgruber, Gerald Wirnsberger, Christoph Klein, Miriam Wöhner, Melanie Kogler, Meinrad Busslinger, Josef M. Penninger, Astrid Hagelkruys, Johannes Stadlmann, Maria Novatchkova, David Hoffmann, Andreas Bergthaler, Georg Schett, Bojan Vilagos, Marion Horrer, Peter Bönelt, Gustav Jonsson, Ulrike Steffen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Glycosylation Immunology Receptors Fc Biology Immunoglobulin G Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Immune system Antigen Loss of Function Mutation Immunology and Allergy Animals Humans Fucosylation Mice Knockout Membrane Proteins Endoplasmic Reticulum Stress Immunity Humoral carbohydrates (lipids) 030104 developmental biology chemistry Humoral immunity Unfolded protein response biology.protein Antibody 030217 neurology & neurosurgery Human Disease Genetics |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 |
| Popis: | Jagn1 deficiency results in alterations in the endoplasmic reticulum (ER) and Golgi apparatus of antibody-producing cells, reduced antibody secretion, and aberrant IgG N-glycosylation. The data uncover a key role for JAGN1 and ER stress in antibody glycosylation and humoral immunity in mice and humans. 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|