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An essential role for the Zn2+ transporter ZIP7 in B cell development

Anzilotti, Consuelo; Swan, David J.; Boisson, Bertrand; Deobagkar-Lele, Mukta; Oliveira, Cathy; 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, Ben; McGrath, John A.; Przyborski, Stefan; Koref, Mauro Santibanez; Tangye, Stuart G.; Werner, Andreas; Rutter, Guy A.; Padilla-Parra, Sergi; Casanova, Jean-Laurent; Cornall, Richard J.; Conley, Mary Ellen; Hambleton, Sophie

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Consuelo Anzilotti

David J. Swan

Bertrand Boisson

Mukta Deobagkar-Lele

Cathy Oliveira

Pauline Chabosseau

Karin R. Engelhardt

Xijin Xu

Rui Chen

Luis Alvarez

Rolando Berlinguer-Palmini

Katherine R. Bull

Eleanor Cawthorne

Adam P. Cribbs

Tanya L. Crockford

Tarana Singh Dang

Amy Fearn

Emma J. Fenech

Sarah J. de Jong

B.Christoffer Lagerholm

Cindy S. Ma

David Sims

Bert van den Berg

Yaobo Xu

Andrew J. Cant

Gary Kleiner

T. Ronan Leahy

M. Teresa de la Morena

Jennifer M. Puck

Ralph S. Shapiro

Mirjam van der Burg

J. Ross Chapman

John C. Christianson

Ben Davies

John A. McGrath

Mauro Santibanez Koref

Stuart G. Tangye

Andreas Werner

Guy A. Rutter

Sergi Padilla-Parra

Jean-Laurent Casanova

Richard J. Cornall

Mary Ellen Conley

Sophie Hambleton


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 Zn2+ in modulating B cell receptor signal strength and positive selection.


Anzilotti, C., Swan, D. J., Boisson, B., Deobagkar-Lele, M., Oliveira, C., Chabosseau, P., …Hambleton, S. (2019). An essential role for the Zn2+ transporter ZIP7 in B cell development. Nature Immunology, 20, 350-361.

Journal Article Type Article
Acceptance Date Dec 5, 2018
Online Publication Date Feb 4, 2019
Publication Date Feb 4, 2019
Deposit Date Jan 15, 2019
Publicly Available Date Aug 4, 2019
Journal Nature Immunology
Print ISSN 1529-2908
Publisher Nature Research
Peer Reviewed Peer Reviewed
Volume 20
Pages 350-361