Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

Marianne Burbage; Selina J Keppler; Francesca Gasparrini; Nuria Martínez-Martín; Mauro Gaya; Christoph Feest; Marie-Charlotte Domart; Cord Herbert Brakebusch; Lucy Collinson; Andreas Bruckbauer; Facundo D Batista

doi:10.1084/jem.20141143

Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

Marianne Burbage, Selina J Keppler, Francesca Gasparrini, Nuria Martínez-Martín, Mauro Gaya, Christoph Feest, Marie-Charlotte Domart, Cord Herbert Brakebusch, Lucy Collinson, Andreas Bruckbauer, Facundo D Batista

41 Citationer (Scopus)

Abstract

The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.

Originalsprog	Engelsk
Tidsskrift	The Journal of Experimental Medicine
Vol/bind	212
Udgave nummer	1
Sider (fra-til)	53-72
ISSN	0022-1007
DOI	https://doi.org/10.1084/jem.20141143
Status	Udgivet - 12 jan. 2015

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10.1084/jem.20141143

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title = "Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity",

abstract = "The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.",

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AU - Burbage, Marianne

AU - Keppler, Selina J

AU - Gasparrini, Francesca

AU - Martínez-Martín, Nuria

AU - Gaya, Mauro

AU - Feest, Christoph

AU - Domart, Marie-Charlotte

AU - Brakebusch, Cord Herbert

AU - Collinson, Lucy

AU - Bruckbauer, Andreas

AU - Batista, Facundo D

PY - 2015/1/12

Y1 - 2015/1/12

N2 - The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.

AB - The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.

U2 - 10.1084/jem.20141143

DO - 10.1084/jem.20141143

M3 - Journal article

C2 - 25547673

SN - 0022-1007

VL - 212

SP - 53

EP - 72

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

IS - 1

ER -

Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

Abstract

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