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

Published in: J Exp Med 2015 Jan; 212(1): 53-72

Authors: Burbage M, Keppler SJ, Gasparrini F, Martínez-Martín N, Gaya M, Feest C, Domart MC, Brakebusch C, Collinson L, Bruckbauer A, Batista FD

Summary

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.

Link to Pubmed [PMID] – 25547673

Link to DOI – 10.1084/jem.20141143