While local physiologic disturbance of the BBB due to stress or infection may precipitate an influx of a sufficient amount of circulating AQP4-IgG to induce astrocytic injury, an alternative explanation, based on our transcriptome and proteome data, is that NMO lesion formation is initiated following the transit of pathologic AQP4-IgG producing B cells to the CNS. The gene discussed is AQP4; the disease is neuromyelitis optica.