Role of B cells and pathogenic autoantibodies in autoimmune CNS and PNS neurologic diseases.

B cells have an ever-increasing role in the etiopathology of a number of autoimmune neurologic disorders, acting, in addition to their autoantibody-secreting role, as antigen-presenting cells but also as sensors, coordinators, and regulators of the immune response. B cells can regulate the immune response, including T-cell activation through antigen presentation, production of proinflammatory cytokines (either as a bystander activation or suppression), and contribution to ectopic lymphoid aggregates. Such important functions make therapeutic depletion of B cells an attractive treatment strategy. The last decade, anti-B-cell therapies targeting B-cell surface molecules, have evolved into a rational approach for successfully treating autoimmune neurologic disorders, even when T cells seem to be the main effector cells, providing an invaluable therapeutic criterion for appreciating the key role of B cells in neurologic autoimmunities. The chapter is focused on the basic aspects of B-cell biology, addresses the different roles of B cells and autoantibodies in the pathogenesis of autoimmune and inflammatory neurologic disorders and highlights how the currently available or in the developmental stage anti-B-cell therapeutics exert their action. It specifically examines the autoantibodies of different IgG-isotypes and IgG-subclasses stressing the uniqueness of IgG4-neuroautoimmunities, and summarizes the current status of the rapidly evolving B-cell therapeutics, including CD19-CAR-T cell therapies, in multiple sclerosis, neuromyelitis-spectrum disorders, autoimmune encephalitis, stiff-person syndrome spectrum disorders, chronic autoimmune neuropathies, myasthenia gravis, and inflammatory myopathies.