RT info:eu-repo/semantics/article
T1 B cell–intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice
A1 Recher, Mike
A1 Burns, Siobhan O.
A1 Fuente García, Miguel Ángel de la
A1 Volpi, Stephano
A1 Dahlberg, Carin
A1 Walter, Jolan E.
A1 Moffitt, Kristin
A1 Mathew, Divij
A1 Honke, Nadine
A1 Lang, Philipp A.
A1 Patrizi, Laura
A1 Falet, Hervé
A1 Keszei, Marton
A1 Mizui, Masayuki
A1 Csizmadia, Eva
A1 Candotti, Fabio
A1 Nadeau, Kari
A1 Bouma, Gerben
A1 Delmonte, Ottavia M.
A1 Frugoni, Francesco
A1 Ferraz Fomini, Angela B.
A1 Buchbinder, David
A1 Lundequist, Emma Maria
A1 Massaad, Michel J.
A1 Tsokos, George C.
A1 Hartwig, John H.
A1 Manis, John
A1 Terhorst, Cox
A1 Geha, Raif S.
A1 Snapper, Scott B.
A1 Lang, Karl S.
A1 Malley, Richard
A1 Westerberg, Lisa S.
A1 Thrasher, Adrian J.
A1 Notarangelo, Luigi D.
K1 B-lymphocytes
K1 Linfocitos B
K1 Wiskott-Aldrich syndrome protein
K1 Proteína del síndrome de Wiskott-Aldrich
K1 Immunoglobulin m
K1 Inmunoglobulina M
K1 Autoantibodies
K1 Autoanticuerpos
AB 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.
PB American Society of Hematology
SN 1528-0020
YR 2012
FD 2012
LK http://uvadoc.uva.es/handle/10324/44636
UL http://uvadoc.uva.es/handle/10324/44636
LA eng
NO Blood, 2012, vol. 119, n. 12. p. 2819-2828
NO Producción Científica
DS UVaDOC
RD 23-nov-2024