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

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 (WIP?ABD), we here investigated the role of WIP binding to actin during B cell activation. We found an altered differentiation of WIP?ABD B cells and diminished antibody affinity maturation after immunization. Mechanistically, WIP?ABD 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. WIP?ABD 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.

SUBMITTER: Keppler SJ 

PROVIDER: S-EPMC6077251 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature