Wiskott-Aldrich Syndrome Interacting Protein Deficiency Uncovers the Role of the Co-receptor CD19 as a Generic Hub for PI3 Kinase Signaling in B Cells

摘要: Humans with Wiskott-Aldrich syndrome display a progressive immunological disorder associated compromised 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 deficiency resulted defects cell homing, chemotaxis, survival, and differentiation, ultimately leading diminished germinal center formation antibody production. Furthermore, the absence WIP, several receptors, namely BCR, BAFFR, CXCR4, CXCR5, CD40, TLR4, were impaired promoting CD19 co-receptor activation subsequent PI3 kinase (PI3K) signaling. The underlying mechanism was due distortion actin tetraspanin networks lead altered surface dynamics. In conclusion, our findings suggest that, by regulating cortical cytoskeleton, influences function general hub for PI3K