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SHR Neuro Cancer Cardio Lipid Metab Microb
Burbage, M; Keppler, SJ; Gasparrini, F; Martínez-Martín, N; Gaya, M; Feest, C; Domart, MC; Brakebusch, C; Collinson, L; Bruckbauer, A; Batista, FD.
Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity.
J Exp Med. 2015; 212(1): 53-72.
Doi: 10.1084/jem.20141143
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- Co-authors Med Uni Graz
- Keppler Selina Jessica
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- Abstract:
- The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-deficient mice are incapable of forming germinal centers or generating plasma B cells upon either viral infection or immunization. Such severe immune deficiency is caused by multiple and profound B cell abnormalities, including early blocks during B cell development; impaired antigen-driven BCR signaling and actin remodeling; defective antigen presentation and in vivo interaction with T cells; and a severe B cell-intrinsic block in plasma cell differentiation. Thus, our study presents a new perspective on Cdc42 as key regulator of B cell physiology.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Antibody Formation - immunology
- B-Lymphocytes - immunology, metabolism, ultrastructure
- Bone Marrow Cells - immunology, metabolism
- Cell Differentiation - genetics, immunology
- Cells, Cultured - administration & dosage
- Flow Cytometry - administration & dosage
- Gene Expression - immunology
- Germinal Center - immunology, metabolism
- Immunity, Humoral - genetics, immunology
- Influenza A virus - immunology
- Lymphoid Tissue - immunology, metabolism
- Mice, Inbred C57BL - administration & dosage
- Mice, Knockout - administration & dosage
- Microscopy, Confocal - administration & dosage
- Microscopy, Electron - administration & dosage
- Orthomyxoviridae Infections - genetics, immunology, virology
- Reverse Transcriptase Polymerase Chain Reaction - administration & dosage
- cdc42 GTP-Binding Protein - genetics, immunology, metabolism