CD20-dependent actin remodelling regulates initial steps of B cell activation

B cells protect us from pathogens by producing neutralising antibodies. The initial step leading to this process is recognition of antigens by B cells. Therefore, understanding what triggers B cell activation upon antigen binding is of great importance for antibody-based immunotherapy and vaccines. B cells are activated by binding to antigens on the surface of an antigen-presenting cell leading to coalescence of B cell receptors into microclusters at the interface between the two cells. The microcluster is a basic signalling platform in B cell activation, allowing the efficient assembly of the membrane proximal B cell receptor signalosome, which triggers intracellular signalling and results in the formation of an immune synapse. One of the proteins implicated in the regulation of B cell activation and nanoscale organisation of the B cell plasma membrane is CD20. CD20 was initially characterised as a putative calcium channel and currently is recognised as an outstanding target for anti-tumour immunotherapy, yet its function during B cell activation remains elusive. Using a reductionist approach and combining high-resolution microscopy with biochemical and pharmacological assays, we demonstrate that CD20 plays a crucial role in regulating actin cytocortex organisation during B cell activation. Cells depleted of CD20 display a striking defect in the cytocortex resulting in formation of membrane blebs, showing dependence on BCR signalling. The effect of CD20 on actin, in turn, modifies the ability of B cell to form microclusters leading to increased B cell activation and aberrant calcium signalling. We characterised changes in actin regulation in B cells lacking CD20. Our preliminary results suggest that CD20 achieves this striking effect by regulating the balance of signalling lipids and B cell metabolism. Thus, our study highlights the role of B cell membrane organisation on actin cytoskeleton and vice versa.