Visualizing a role for the actin cytoskeleton in the regulation of B-cell activation.

Appropriate activation of B cells is required for mounting protective humoral immune responses. B-cell activation is initiated following specific recognition of antigen by the B-cell receptor (BCR) and results in the generation of antibody-secreting plasma cells and long-lived memory cells. Initial imaging approaches revealed that B cells undergo dramatic molecular and morphological reorganizations following recognition of antigen. A number of these studies pointed to a role for the underlying cytoskeleton in regulating early events of B-cell activation. More recently, groundbreaking advances in imaging technologies have enabled direct visualization of the role for the cytoskeleton in regulating events at the B-cell membrane. Indeed, we have demonstrated that an ezrin-defined actin network shapes BCR diffusion and signaling both in the resting state and following antigen-induced activation. Importantly, alongside these in vitro imaging approaches, it has been demonstrated that mutations in cytoskeleton regulators such as CD19, dedicator of cytokinesis 8 (DOCK8), and Wiskott-Aldrich syndrome protein (WASp) are often associated with antibody deficiency syndromes in humans, establishing the importance of cytoskeleton reorganizations in conferring effective adaptive immunity.