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Título
B cell–intrinsic deficiency of the Wiskott-Aldrich syndrome protein (WASp) causes severe abnormalities of the peripheral B-cell compartment in mice
Autor
Año del Documento
2012
Editorial
American Society of Hematology
Descripción
Producción Científica
Documento Fuente
Blood, 2012, vol. 119, n. 12. p. 2819-2828
Resumen
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.
Palabras Clave
B-lymphocytes
Linfocitos B
Wiskott-Aldrich syndrome protein
Proteína del síndrome de Wiskott-Aldrich
Immunoglobulin m
Inmunoglobulina M
Autoantibodies
Autoanticuerpos
ISSN
1528-0020
Revisión por pares
SI
Patrocinador
National Institutes of Health (grant 2PO1HL059561-11-A1)
Swiss National Science Foundation (grant PASMP3-127678)
Instituto de Salud Carlos III (grant PI10/ 02 511)
Junta de Castilla y León (grant VA244A11-2)
Swiss National Science Foundation (grant PASMP3-127678)
Instituto de Salud Carlos III (grant PI10/ 02 511)
Junta de Castilla y León (grant VA244A11-2)
Version del Editor
Propietario de los Derechos
© 2012 American Society of Hematology
Idioma
eng
Tipo de versión
info:eu-repo/semantics/publishedVersion
Derechos
openAccess
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