The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses

Summary: Wiskott-Aldrich syndrome protein (WASp) is a main cytoskeletal regulator in B cells. WASp-interacting protein (WIP) binds to and stabilizes WASp but also interacts with actin. Using mice with a mutated actin binding domain of WIP (WIPΔABD), we here investigated the role of WIP binding to ac...

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Main Authors:	Selina Jessica Keppler, Marianne Burbage, Francesca Gasparrini, Lara Hartjes, Shweta Aggarwal, Michel J. Massaad, Raif S. Geha, Andreas Bruckbauer, Facundo D. Batista
Format:	Article
Language:	English
Published:	Elsevier 2018-07-01
Series:	Cell Reports
Online Access:	http://www.sciencedirect.com/science/article/pii/S2211124718309616

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spelling	doaj-a8e1adbe9bb743a7bee7ea3fae541c3a2020-11-25T01:46:35ZengElsevierCell Reports2211-12472018-07-01243619629The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune ResponsesSelina Jessica Keppler0Marianne Burbage1Francesca Gasparrini2Lara Hartjes3Shweta Aggarwal4Michel J. Massaad5Raif S. Geha6Andreas Bruckbauer7Facundo D. Batista8Lymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UK; MRI, TranslaTUM, Institute for Clinical Chemistry and Pathobiochemistry, Immune Signals and Cancer, 81675 Munich, Germany; Corresponding authorLymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UKLymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UKMRI, TranslaTUM, Institute for Clinical Chemistry and Pathobiochemistry, Immune Signals and Cancer, 81675 Munich, GermanyLymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UKDivision of Immunology, Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USADivision of Immunology, Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USALymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UKLymphocyte Interaction Laboratory, Francis Crick Institute, London NW1 1AT, UK; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USASummary: Wiskott-Aldrich syndrome protein (WASp) is a main cytoskeletal regulator in B cells. WASp-interacting protein (WIP) binds to and stabilizes WASp but also interacts with actin. Using mice with a mutated actin binding domain of WIP (WIPΔABD), we here investigated the role of WIP binding to actin during B cell activation. We found an altered differentiation of WIPΔABD B cells and diminished antibody affinity maturation after immunization. Mechanistically, WIPΔABD B cells showed impaired B cell receptor (BCR)-induced PI3K signaling and actin reorganization, likely caused by diminished CD81 expression and altered CD19 dynamics on the B cell surface. WIPΔABD B cells displayed reduced in vivo motility, concomitantly with impaired chemotaxis and defective F-actin polarization, HS1 phosphorylation, and polarization of HS1 to F-actin-rich structures after CXCL12 stimulation in vitro. We thus concluded that WIP binding to actin, independent of its binding to WASp, is critical for actin cytoskeleton plasticity in B cells. : The absence of WIP in mouse and human triggers immunodeficiency mimicking Wiskott-Aldrich syndrome. Keppler et al. report that binding of WIP to actin shapes actin cytoskeleton plasticity in B cells; is sufficient to modulate signaling, chemotaxis, and in vivo migration; and hence influences humoral immune responses. Keywords: B lymphocytes, chemotaxis, actin cytoskeleton, CXCR4, HS1, Wiskott-Aldrich syndrome, PI3K signalinghttp://www.sciencedirect.com/science/article/pii/S2211124718309616
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Selina Jessica Keppler Marianne Burbage Francesca Gasparrini Lara Hartjes Shweta Aggarwal Michel J. Massaad Raif S. Geha Andreas Bruckbauer Facundo D. Batista
spellingShingle	Selina Jessica Keppler Marianne Burbage Francesca Gasparrini Lara Hartjes Shweta Aggarwal Michel J. Massaad Raif S. Geha Andreas Bruckbauer Facundo D. Batista The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses Cell Reports
author_facet	Selina Jessica Keppler Marianne Burbage Francesca Gasparrini Lara Hartjes Shweta Aggarwal Michel J. Massaad Raif S. Geha Andreas Bruckbauer Facundo D. Batista
author_sort	Selina Jessica Keppler
title	The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses
title_short	The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses
title_full	The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses
title_fullStr	The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses
title_full_unstemmed	The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses
title_sort	lack of wip binding to actin results in impaired b cell migration and altered humoral immune responses
publisher	Elsevier
series	Cell Reports
issn	2211-1247
publishDate	2018-07-01
description	Summary: Wiskott-Aldrich syndrome protein (WASp) is a main cytoskeletal regulator in B cells. WASp-interacting protein (WIP) binds to and stabilizes WASp but also interacts with actin. Using mice with a mutated actin binding domain of WIP (WIPΔABD), we here investigated the role of WIP binding to actin during B cell activation. We found an altered differentiation of WIPΔABD B cells and diminished antibody affinity maturation after immunization. Mechanistically, WIPΔABD B cells showed impaired B cell receptor (BCR)-induced PI3K signaling and actin reorganization, likely caused by diminished CD81 expression and altered CD19 dynamics on the B cell surface. WIPΔABD B cells displayed reduced in vivo motility, concomitantly with impaired chemotaxis and defective F-actin polarization, HS1 phosphorylation, and polarization of HS1 to F-actin-rich structures after CXCL12 stimulation in vitro. We thus concluded that WIP binding to actin, independent of its binding to WASp, is critical for actin cytoskeleton plasticity in B cells. : The absence of WIP in mouse and human triggers immunodeficiency mimicking Wiskott-Aldrich syndrome. Keppler et al. report that binding of WIP to actin shapes actin cytoskeleton plasticity in B cells; is sufficient to modulate signaling, chemotaxis, and in vivo migration; and hence influences humoral immune responses. Keywords: B lymphocytes, chemotaxis, actin cytoskeleton, CXCR4, HS1, Wiskott-Aldrich syndrome, PI3K signaling
url	http://www.sciencedirect.com/science/article/pii/S2211124718309616
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The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses

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