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

Cell Reports
Selina J KepplerFacundo D Batista

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.

Citations

Dec 12, 2018·Journal of Leukocyte Biology·Karla F Castro-OchoaMichael Schnoor
Mar 22, 2019·Frontiers in Immunology·Minghui He, Lisa S Westerberg
Dec 20, 2018·Immunological Reviews·Erin Janssen, Raif S Geha
Jun 1, 2021·Frontiers in Cell and Developmental Biology·Jorge Ibañez-VegaMaría Isabel Yuseff

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
ELISA
fluorescence-activated
FCS

Software Mentioned

ImageJ
Prism
Zen
Excel
Imaris
Cell R
FlowJo
MATLAB

Related Concepts

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

B cell Activation

B cell activation is initiated by the ligation of the B cell receptor with antigen and ultimately results in the production of protective antibodies against potentially pathogenic invaders. Here is the latest research.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.