PMID:22411869

Citation	Westerberg, LS, Dahlberg, C, Baptista, M, Moran, CJ, Detre, C, Keszei, M, Eston, MA, Alt, FW, Terhorst, C, Notarangelo, LD and Snapper, SB (2012) Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function. Blood 119:3966-74
Abstract	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.
Links	PubMed PMC3350364 Online version:10.1182/blood-2010-09-308197
Keywords	Animals; B-Lymphocytes/cytology; B-Lymphocytes/physiology; Blotting, Western; Cell Movement; Cell Proliferation; Cells, Cultured; Chemotaxis; Ficoll/analogs & derivatives; Ficoll/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
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:DAB2	acts_upstream_of_or_within	GO:0007492: endoderm development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.