The Lack of WIP Binding to Actin Results in Impaired B Cell Migration and Altered Humoral Immune Responses.
Cell Rep
; 24(3): 619-629, 2018 07 17.
Article
em En
| MEDLINE
| ID: mdl-30021160
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Movimento Celular
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Actinas
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Imunidade Humoral
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article