B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice

Détails

ID Serval
serval:BIB_118932EEEB25
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
B cell-intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice
Périodique
Blood
Auteur(s)
Recher M., Burns S. O., de la Fuente M. A., Volpi S., Dahlberg C., Walter J. E., Moffitt K., Mathew D., Honke N., Lang P. A., Patrizi L., Falet H., Keszei M., Mizui M., Csizmadia E., Candotti F., Nadeau K., Bouma G., Delmonte O. M., Frugoni F., Fomin A. B., Buchbinder D., Lundequist E. M., Massaad M. J., Tsokos G. C., Hartwig J., Manis J., Terhorst C., Geha R. S., Snapper S., Lang K. S., Malley R., Westerberg L., Thrasher A. J., Notarangelo L. D.
ISSN
1528-0020 (Electronic)
ISSN-L
0006-4971
Statut éditorial
Publié
Date de publication
2012
Volume
119
Numéro
12
Pages
2819-28
Langue
anglais
Notes
Recher, Mike
Burns, Siobhan O
de la Fuente, Miguel A
Volpi, Stefano
Dahlberg, Carin
Walter, Jolan E
Moffitt, Kristin
Mathew, Divij
Honke, Nadine
Lang, Philipp A
Patrizi, Laura
Falet, Herve
Keszei, Marton
Mizui, Masayuki
Csizmadia, Eva
Candotti, Fabio
Nadeau, Kari
Bouma, Gerben
Delmonte, Ottavia M
Frugoni, Francesco
Fomin, Angela B Ferraz
Buchbinder, David
Lundequist, Emma Maria
Massaad, Michel J
Tsokos, George C
Hartwig, John
Manis, John
Terhorst, Cox
Geha, Raif S
Snapper, Scott
Lang, Karl S
Malley, Richard
Westerberg, Lisa
Thrasher, Adrian J
Notarangelo, Luigi D
eng
090233/Wellcome Trust/United Kingdom
P01 HL059561/HL/NHLBI NIH HHS/
2P01HL059561-11-A1/HL/NHLBI NIH HHS/
Wellcome Trust/United Kingdom
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Blood. 2012 Mar 22;119(12):2819-28. doi: 10.1182/blood-2011-09-379412. Epub 2012 Feb 1.
Résumé
Wiskott Aldrich syndrome (WAS) is caused by mutations in the WAS gene that encodes for a protein (WASp) involved in cytoskeleton organization in hematopoietic cells. Several distinctive abnormalities of T, B, and natural killer lymphocytes; dendritic cells; and phagocytes have been found in WASp-deficient patients and mice; however, the in vivo consequence of WASp deficiency within individual blood cell lineages has not been definitively evaluated. By conditional gene deletion we have generated mice with selective deficiency of WASp in the B-cell lineage (B/WcKO mice). We show that this is sufficient to cause a severe reduction of marginal zone B cells and inability to respond to type II T-independent Ags, thereby recapitulating phenotypic features of complete WASp deficiency. In addition, B/WcKO mice showed prominent signs of B-cell dysregulation, as indicated by an increase in serum IgM levels, expansion of germinal center B cells and plasma cells, and elevated autoantibody production. These findings are accompanied by hyperproliferation of WASp-deficient follicular and germinal center B cells in heterozygous B/WcKO mice in vivo and excessive differentiation of WASp-deficient B cells into class-switched plasmablasts in vitro, suggesting that WASp-dependent B cell-intrinsic mechanisms critically contribute to WAS-associated autoimmunity.
Mots-clé
Animals, Autoantibodies/blood/immunology, Autoantigens/immunology, B-Lymphocytes/*cytology/*immunology, Cell Count, Disease Models, Animal, Flow Cytometry, Fluorescent Antibody Technique, Mice, Mice, Inbred C57BL, Mice, Knockout, Wiskott-Aldrich Syndrome Protein/deficiency/genetics/*immunology
Pubmed
Open Access
Oui
Création de la notice
01/11/2017 10:29
Dernière modification de la notice
20/08/2019 12:39
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