title: Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity.
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.
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Marianne
authors.initials: M
authors.lastname: Burbage
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Selina J
authors.initials: SJ
authors.lastname: Keppler
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Gasparrini
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Nuria
authors.initials: N
authors.lastname: Martínez-Martín
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Mauro
authors.initials: M
authors.lastname: Gaya
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Christoph
authors.initials: C
authors.lastname: Feest
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Domart
authors.affiliation: Biomedical Institute, Biotech Research and Innovation Centre, University of Copenhagen, 2100 Copenhagen, Denmark.
authors.forename: Cord
authors.initials: C
authors.lastname: Brakebusch
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Lucy
authors.initials: L
authors.lastname: Collinson
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bruckbauer
authors.affiliation: Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK facundo.batista@cancer.org.uk.
authors.forename: Facundo D
authors.initials: FD
authors.lastname: Batista
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D056724:Immunity, Humoral / Q000235:genetics / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C581598:Cdc42 protein, mouse; D020764:cdc42 GTP-Binding Protein