期刊
CELL REPORTS
卷 24, 期 3, 页码 619-629出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.06.051
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资金
- Francis Crick Institute - Cancer Research UK [FC001035, FC001136]
- UK Medical Research Council [FC001035, FC001136]
- Wellcome Trust [FC001035, FC001136]
- Institute Pasteur-Fondazione Cenci Bolognetti
- German Research Foundation (DFG) [Ke1737/1-1, Ke1737/2-1]
- Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery of the NIH [UM1AI100663]
- Phillip T. and Susan M. Ragon Institute Foundation
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 (WIP Delta ABD), we here investigated the role of WIP binding to actin during B cell activation. We found an altered differentiation of WIPDABD B cells and diminished antibody affinity maturation after immunization. Mechanistically, WIPDABD 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. WIPDABD 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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