Schematic targets of MS treatments upon CNS compartmentalized inflammation, especially in tertiary lymphoid organs (TLO). Except for natalizumab (owing to unclear mechanisms), none of the treatments targeting blood B-cells have shown any action upon intrathecal IgG synthesis. Preliminary results suggest that rituximab also fails to reduce IgG synthesis. Future treatment strategies might be redirected to reset all the components of intrathecally compartmentalized inflammation. APC: antigen-presenting cells; BMT: bone marrow transplant; PB/PC: plasmablasts/plasma cells; TLO: tertiary lymphoid organs.