We investigate molecular mechanisms of B cell activation that regulate humoral immunity and pathogenesis of B cell-mediated diseases. B cells migrate in and out of circulation and lymphoid tissues and respond to environmental cues by recognizing antigens and engaging with other components of the immune system. This requires them to undergo considerable morphological, molecular and cytoskeletal reorganization. Dynamic remodeling of the B cell membrane and the actin cytoskeleton facilitates subcellular organization of key signaling proteins, enabling B cells to accomplish their various functions. We employ high-resolution live cell imaging, quantitative systems biology methods and genetic knockouts in mice to investigate the role of membrane-cytoskeleton remodeling proteins in regulating B cell function. We have discovered that Ezrin, a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-cytoskeleton linkers, regulates multiple facets of B cell function, such as proliferation, differentiation, migration, and antibody production. We recently discovered that Ezrin plays an important role in regulating B cell autoimmunity, inflammation, and cancer. We are currently investigating the molecular mechanisms underlying these diverse functions of Ezrin in B cell immunity and pathogenesis.