While anti-AQP-4 antibodies are thought to be pathogenic in NMOSD, the observation that decreased NMO relapses seen following anti-CD20-mediated B-cell depletion do not correlate well with changes in anti-AQP4 antibody titers (134–136), indicates that the role of B cells in NMO may extend beyond antibody production. Here, AQP4 is linked to neuromyelitis optica.