2024-03-29T07:43:41Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/98242021-06-23T09:49:16Zcom_10324_1133com_10324_931com_10324_894col_10324_1209
WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function.
Westerberg, Lisa S.
Wermeling, Fredrik
Ochs, Hans D.
Karlsson, Mikael C. I.
Snapper, Scott B.
Notarangelo, Luigi D.
Fuente García, Miguel Ángel de la
Células hematopoyéticas
Producción Científica
Development of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4(+) and CD8(+) T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP(-/-) mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of "natural" IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance.
2015-03-23T08:37:40Z
2015-03-23T08:37:40Z
2008
info:eu-repo/semantics/article
Blood. 2008 Nov 15;112(10):4139-47
0006-4971
http://uvadoc.uva.es/handle/10324/9824
10.1182/blood-2008-02-140715
4139
10
4147
Blood
112
spa
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
American Society of Hematology
https://uvadoc.uva.es/bitstream/10324/9824/6/6%20M.A.%20de%20la%20Fuente%20PD-219.pdf.jpg
Hispana
TEXT
http://creativecommons.org/licenses/by-nc-nd/4.0/
UVaDOC. Repositorio Documental de la Universidad de Valladolid
http://uvadoc.uva.es/handle/10324/9824