Co-localization of the terminal complement complex (TCC) with an NMO patient's serum AQP4-IgG. A. The heat-inactivated serum sample of an AQP4-IgG positive NMO patient (titer 1:5,120) was added to M23 AQP4 transfected cells (without EmGFP fusion protein) in the presence of either active or inactive complement. Complement-mediated cytotoxicity (TCC, green) was only detectable after addition of active complement. Furthermore, the TCC co-localized (merged) with the antibodies directed to AQP4 (AQP4-IgG, red) resulting in lysis of the AQP4 transfected cells (DAPI staining, blue). The activation of the complement cascade was accompanied by an internalization of AQP4-IgG, resulting in an attenuated signal (red). B. An AQP4-IgG negative serum sample of an SLE patient resulted in no formation of the TCC in the presence of active complement.