An essential role for the Zn transporter ZIP7 in B cell development.
Clicks: 290
ID: 56301
2019
Article Quality & Performance Metrics
Overall Quality
Improving Quality
0.0
/100
Combines engagement data with AI-assessed academic quality
Reader Engagement
Emerging Content
8.7
/100
29 views
29 readers
Trending
AI Quality Assessment
Not analyzed
Abstract
Despite the known importance of zinc for human immunity, molecular insights into its roles have remained limited. Here we report a novel autosomal recessive disease characterized by absent B cells, agammaglobulinemia and early onset infections in five unrelated families. The immunodeficiency results from hypomorphic mutations of SLC39A7, which encodes the endoplasmic reticulum-to-cytoplasm zinc transporter ZIP7. Using CRISPR-Cas9 mutagenesis we have precisely modeled ZIP7 deficiency in mice. Homozygosity for a null allele caused embryonic death, but hypomorphic alleles reproduced the block in B cell development seen in patients. B cells from mutant mice exhibited a diminished concentration of cytoplasmic free zinc, increased phosphatase activity and decreased phosphorylation of signaling molecules downstream of the pre-B cell and B cell receptors. Our findings highlight a specific role for cytosolic Zn in modulating B cell receptor signal strength and positive selection.
| Reference Key |
anzilotti2019annature
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Anzilotti, Consuelo;Swan, David J;Boisson, Bertrand;Deobagkar-Lele, Mukta;Oliveira, Catarina;Chabosseau, Pauline;Engelhardt, Karin R;Xu, Xijin;Chen, Rui;Alvarez, Luis;Berlinguer-Palmini, Rolando;Bull, Katherine R;Cawthorne, Eleanor;Cribbs, Adam P;Crockford, Tanya L;Dang, Tarana Singh;Fearn, Amy;Fenech, Emma J;de Jong, Sarah J;Lagerholm, B Christoffer;Ma, Cindy S;Sims, David;van den Berg, Bert;Xu, Yaobo;Cant, Andrew J;Kleiner, Gary;Leahy, T Ronan;de la Morena, M Teresa;Puck, Jennifer M;Shapiro, Ralph S;van der Burg, Mirjam;Chapman, J Ross;Christianson, John C;Davies, Benjamin;McGrath, John A;Przyborski, Stefan;Santibanez Koref, Mauro;Tangye, Stuart G;Werner, Andreas;Rutter, Guy A;Padilla-Parra, Sergi;Casanova, Jean-Laurent;Cornall, Richard J;Conley, Mary Ellen;Hambleton, Sophie; |
| Journal | Nature Immunology |
| Year | 2019 |
| DOI |
10.1038/s41590-018-0295-8
|
| URL | |
| Keywords |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.