A crucial role for Jagunal homolog 1 in humoral immunity and antibody glycosylation in mice and humans.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
04 01 2021
04 01 2021
Historique:
received:
25
03
2020
revised:
17
07
2020
accepted:
18
08
2020
entrez:
15
9
2020
pubmed:
16
9
2020
medline:
31
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32930709
pii: 152087
doi: 10.1084/jem.20200559
pmc: PMC7953624
pii:
doi:
Substances chimiques
Immunoglobulin G
0
JAGN1 protein, human
0
Membrane Proteins
0
Receptors, Fc
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Austrian Science Fund FWF
ID : Z 271
Pays : Austria
Informations de copyright
© 2020 Hagelkruys et al.
Déclaration de conflit d'intérêts
Disclosures: The authors declare no competing interests exist.
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