Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Keppler, SJ; Gasparrini, F; Burbage, M; Aggarwal, S; Frederico, B; Geha, RS; Way, M; Bruckbauer, A; Batista, FD.
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.
Immunity. 2015; 43(4): 660-73.
Doi: 10.1016/j.immuni.2015.09.004
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Keppler Selina Jessica
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Actin Cytoskeleton - ultrastructure
- Actins - analysis
- Animals - administration & dosage
- Antibody Formation - administration & dosage
- Antigens, CD19 - physiology
- B-Lymphocytes - drug effects, enzymology, immunology, ultrastructure
- Carrier Proteins - genetics, physiology
- Cells, Cultured - administration & dosage
- Chemokines - pharmacology, physiology
- Chemotaxis - drug effects
- Cytoskeletal Proteins - administration & dosage
- Germinal Center - immunology, pathology
- Haptens - administration & dosage
- Hemocyanins - pharmacology
- Lymphocyte Activation - drug effects
- Lymphopoiesis - administration & dosage
- Membrane Proteins - immunology
- Mice - administration & dosage
- Phosphatidylinositol 3-Kinases - physiology
- Phosphorylation - administration & dosage
- Plasma Cells - immunology
- Protein Processing, Post-Translational - administration & dosage
- Radiation Chimera - administration & dosage
- Receptors, Antigen, B-Cell - immunology
- Receptors, Chemokine - physiology
- Signal Transduction - immunology
- Tetraspanins - analysis
- Vaccinia - immunology, pathology