Document Detail


Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function.
MedLine Citation:
PMID:  22411869     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Wiskott-Aldrich syndrome protein (WASP) is a key cytoskeletal regulator of hematopoietic cells. Although WASP-knockout (WKO) mice have aberrant B-cell cytoskeletal responses, B-cell development is relatively normal. We hypothesized that N-WASP, a ubiquitously expressed homolog of WASP, may serve some redundant functions with WASP in B cells. In the present study, we generated mice lacking WASP and N-WASP in B cells (conditional double knockout [cDKO] B cells) and show that cDKO mice had decreased numbers of follicular and marginal zone B cells in the spleen. Receptor-induced activation of cDKO B cells led to normal proliferation but a marked reduction of spreading compared with wild-type and WKO B cells. Whereas WKO B cells showed decreased migration in vitro and homing in vivo compared with wild-type cells, cDKO B cells showed an even more pronounced decrease in the migratory response in vivo. After injection of 2,4,6-trinitrophenol (TNP)-Ficoll, cDKO B cells had reduced antigen uptake in the splenic marginal zone. Despite high basal serum IgM, cDKO mice mounted a reduced immune response to the T cell-independent antigen TNP-Ficoll and to the T cell-dependent antigen TNP-keyhole limpet hemocyanin. Our results reveal that the combined activity of WASP and N-WASP is required for peripheral B-cell development and function.
Authors:
Lisa S Westerberg; Carin Dahlberg; Marisa Baptista; Christopher J Moran; Cynthia Detre; Marton Keszei; Michelle A Eston; Frederick W Alt; Cox Terhorst; Luigi D Notarangelo; Scott B Snapper
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-12
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-07-12     Revised Date:  2014-10-24    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3966-74     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / cytology*,  physiology*
Blotting, Western
Cell Movement
Cell Proliferation
Cells, Cultured
Chemotaxis
Ficoll / analogs & derivatives,  pharmacology
Flow Cytometry
Hematopoiesis / physiology
Immunization
Immunoenzyme Techniques
Integrases / metabolism
Mice
Mice, Knockout
Trinitrobenzenes / pharmacology
Wiskott-Aldrich Syndrome Protein / physiology*
Wiskott-Aldrich Syndrome Protein, Neuronal / physiology*
Grant Support
ID/Acronym/Agency:
2P30DK034854-26/DK/NIDDK NIH HHS; AI-076210/AI/NIAID NIH HHS; AI-50950/AI/NIAID NIH HHS; DK-43351/DK/NIDDK NIH HHS; HL-59561/HL/NHLBI NIH HHS; P30 DK043351/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/TNP-ficoll; 0/Trinitrobenzenes; 0/Was protein, mouse; 0/Wasl protein, mouse; 0/Wiskott-Aldrich Syndrome Protein; 0/Wiskott-Aldrich Syndrome Protein, Neuronal; 25702-74-3/Ficoll; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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