Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function

Westerberg, Lisa S.; Dahlberg, Carin; Baptista, Marisa A. P.; Moran, Christopher J.; Detre, Cynthia; Keszei, Márton; Eston, Michelle A.; Alt, Frederick W.; Terhorst, Cox; Notarangelo, Luigi D.; Snapper, Scott B.

doi:10.1182/blood-2010-09-308197

Cited by 72 publications

(82 citation statements)

References 34 publications

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“…(B) Quantification of CXCL12 mRNA in spleen cells (B) and in BM (C) in the steady-state (n=5). *P value < 0.05, **P value < 0.01, ***P value < 0.001. have only been recently fully appreciated 19 and include defective B-cell homing to the spleen 36 as we report here. Such defective B-cell homing may partly explain the marked B lymphopenia that is observed in the steadystate in adult WKO mice.…”

Section: Discussionmentioning

confidence: 79%

Wiskott-Aldrich syndrome protein-deficient hematopoietic cells can be efficiently mobilized by granulocyte colony-stimulating factor

Charrier

Blundell²,

Cédrone

et al. 2013

Haematologica

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Section: Discussionmentioning

confidence: 79%

Wiskott-Aldrich syndrome protein-deficient hematopoietic cells can be efficiently mobilized by granulocyte colony-stimulating factor

Charrier

Blundell²,

Cédrone

et al. 2013

Haematologica

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“…However, simultaneous deletion of both WAS and WASL abrogates antigen-induced B cell responses, suggesting that while these proteins have non-redundant negative functions, they also act redundantly to promote B cell activation 36,37 . Surprisingly, while the absence of WAS reduces the amount of cortical actin and impairs the structure of immune synapses 7,34,35 , the absence of WASL increases the amount of actin in B cell synapses 35 , suggesting that their role in actin polymerization is also distinct.…”

Section: [H1] Structure Of the Cortical Cytoskeletonmentioning

confidence: 99%

Cytoskeletal control of B cell responses to antigens

Tolar

2017

Nat Rev Immunol

125

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The actin cytoskeleton is essential for cell mechanics and has increasingly been implicated in the regulation of cell signalling. In B cells, the actin cytoskeleton couples extensively to B cell receptor (BCR) signalling pathways and its defects can either enhance or suppress B cell activation. Recent insights from single-cell imaging and biophysical techniques suggest that actin orchestrates BCR signalling at the plasma membrane through effects on protein diffusion, and that it regulates antigen discrimination through the biomechanics of immune synapses. These mechanical functions also play a role in the adaptation of B cell subsets to specialized tasks during antibody responses.3

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“…6 Similar to WASP, N-WASP undergoes a conformational change upon activation that enables initiation of actin polymerization, 7,8 thereby linking cellular activation to cytoskeletal modifications. 9 Selective deletion of N-WASP in B lymphocytes of Was knockout (WKO) mice resulted in the aggravation of B-cell abnormalities, including a strong decrease of intracellular calcium flux and Bruton's tyrosine kinase (Btk) and Src homology 2-containing inositol 59 phosphatase phosphorylation upon B-cell receptor (BCR) stimulation, 10 further worsening of MZ B-cell depletion, 11 and defective somatic hypermutation. 12 However, lack of WASP expression in multiple hematopoietic cells may have indirectly contributed to B-cell abnormalities in these models.…”

Section: Introductionmentioning

confidence: 99%

N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome

Volpi

Santori

Abernethy

et al. 2016

Blood

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By generating a mouse lacking expression of the WAS protein (WASP) selectively in B lymphocytes (B/WcKO), we and others have revealed a nonredundant B-cell-intrinsic role of WASP in immune homeostasis and prevention of autoimmunity, as well as in marginal zone (MZ) development and regulation of the germinal center (GC) reaction.3-5 Neural WASP (N-WASP, encoded by the Wasl gene) is another member of the WASP family of proteins; it is ubiquitously expressed and shares 50% homology with WASP.6 Similar to WASP, N-WASP undergoes a conformational change upon activation that enables initiation of actin polymerization, 7,8 thereby linking cellular activation to cytoskeletal modifications. 9 Selective deletion of N-WASP in B lymphocytes of Was knockout (WKO) mice resulted in the aggravation of B-cell abnormalities, including a strong decrease of intracellular calcium flux and Bruton's tyrosine kinase (Btk) and Src homology 2-containing inositol 59 phosphatase phosphorylation upon B-cell receptor (BCR) stimulation, 10 further worsening of MZ B-cell depletion, 11 and defective somatic hypermutation. 12 However, lack of WASP expression in multiple hematopoietic cells may have indirectly contributed to B-cell abnormalities in these models.To investigate the B-cell intrinsic role played by WASP and N-WASP in immune homeostasis and regulation more specifically, we have developed a double conditional mouse model (B/DcKO) in which deletion of both Was and Wasl floxed alleles in B lymphocytes is driven by the Cre recombinase expressed under the B-cell-specific promoter mb1. Here we show that deletion of N-WASP in B cells impairs B-cell activation and T-cell-dependent antibody responses and

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Wiskott-Aldrich syndrome protein (WASP) and N-WASP are critical for peripheral B-cell development and function

Cited by 72 publications

References 34 publications

Wiskott-Aldrich syndrome protein-deficient hematopoietic cells can be efficiently mobilized by granulocyte colony-stimulating factor

Wiskott-Aldrich syndrome protein-deficient hematopoietic cells can be efficiently mobilized by granulocyte colony-stimulating factor

Cytoskeletal control of B cell responses to antigens

N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome

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