Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

  • J Exp Med. 2015 Jan 12;212(1):53-72. doi: 10.1084/jem.20141143.
Marianne Burbage  1 ,  Selina J Keppler  1 ,  Francesca Gasparrini  1 ,  Nuria Martínez-Martín  1 ,  Mauro Gaya  1 ,  Christoph Feest  1 ,  Marie-Charlotte Domart  1 ,  Cord Brakebusch  2 ,  Lucy Collinson  1 ,  Andreas Bruckbauer  1 ,  Facundo D Batista  3
Affiliations
  • 1. Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK.
  • 2. Biomedical Institute, Biotech Research and Innovation Centre, University of Copenhagen, 2100 Copenhagen, Denmark.
  • 3. Lymphocyte Interaction Laboratory, Electron Microscopy Unit, London Research Institute, Cancer Research UK, London WC2A 3LY, England, UK [email protected].
PMID: 25547673 DOI: 10.1084/jem.20141143
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.

Products