Journal
IMMUNITY
Volume 43, Issue 4, Pages 660-673Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2015.09.004
Keywords
-
Categories
Funding
- Francis Crick Institute
- German Research Foundation (DFG) [Ke1737/1-1]
- Institute Pasteur-Fondazione Cenci Bolognetti
- long-term EMBO fellowship
- Royal Society Wolfson Research Merit Award
- Cancer Research UK [15691] Funding Source: researchfish
- The Francis Crick Institute [10035] Funding Source: researchfish
Ask authors/readers for more resources
Humans with Wiskott-Aldrich syndrome display a progressive immunological disorder associated with compromised Wiskott-Aldrich Syndrome Interacting Protein (WIP) function. Mice deficient in WIP recapitulate such an immunodeficiency that has been attributed to T cell dysfunction; however, any contribution of B cells is as yet undefined. Here we have shown that WIP deficiency resulted in defects in B cell homing, chemotaxis, survival, and differentiation, ultimately leading to diminished germinal center formation and antibody production. Furthermore, in the absence of WIP, several receptors, namely the BCR, BAFFR, CXCR4, CXCR5, CD40, and TLR4, were impaired in promoting CD19 co-receptor activation and subsequent PI3 kinase (PI3K) signaling. The underlying mechanism was due to a distortion in the actin and tetraspanin networks that lead to altered CD19 cell surface dynamics. In conclusion, our findings suggest that, by regulating the cortical actin cytoskeleton, WIP influences the function of CD19 as a general hub for PI3K signaling.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available