Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Marianne Burbage, Selina J Keppler, Francesca Gasparrini, Nuria Martínez-Martín, Mauro Gaya, Christoph Feest, Marie-Charlotte Domart, Cord Herbert Brakebusch, Lucy Collinson, Andreas Bruckbauer, Facundo D Batista
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.
|Tidsskrift||The Journal of Experimental Medicine|
|Status||Udgivet - 2015|