WHAMM deficiency alters splenic B-cell populations, BCR signaling, and actin remodeling

Members of the Wiskott-Aldrich syndrome protein (WASP) family orchestrate cytoskeletal reorganization that modulates B-cell receptor (BCR) signaling and B-cell fate decisions. WHAMM, a WASP-family nucleation-promoting factor member that associates with actin, membranes and microtubules, has not been functionally characterized in B cells. To investigate the role of WHAMM in B-cell development and function, we analyzed a conditional mouse model in which Whamm was deleted in the B-cell lineage. WHAMM-deficient mice exhibited altered splenic B-cell composition, characterized by an accumulation of splenic transitional B cells and a reduction of follicular B cells. Meanwhile, WHAMM deficiency altered the spatial organization and kinetics of proximal BCR signaling, and modified the dynamics of BCR-induced actin remodeling. However, WHAMM-deficient B cells showed largely preserved BCR internalization, antigen presentation, PI3K-AKT-mTOR signaling, ROS production, and mitochondrial membrane potential. Together, this work indicates that WHAMM helps shape splenic B-cell populations and regulates proximal BCR signaling and actin dynamics, while several downstream functional responses remain largely preserved in this study.