CD59 efficiently protects human NT2-N neurons against complement-mediated damage

Scand J Immunol. 2007 Aug-Sep;66(2-3):345-51. doi: 10.1111/j.1365-3083.2007.01959.x.


The complement regulatory protein CD59 controls cell survival by the inhibition of C5b-9 formation on the cell membrane. Loss of CD59 increases the susceptibility of cells to complement-mediated damage and lysis. Deposition of IgM can induce complement activation with subsequent cell death. We have previously demonstrated the presence of CD59 on human NT2-N neurons. In this study, we investigated the functional role of CD59 for NT2-N cell survival after IgM-mediated complement activation. Complement activation was induced on NT2-N neurons with human serum following incubation with the IgM monoclonal antibody A2B5 reacting with a neuronal cell membrane epitope. Deposition of C1q and C5b-9 was detected on the cell membrane and sC5b-9 in the culture supernatant. Specific inhibition of complement was obtained by the C3 inhibitor compstatin, and by anti-C5/C5a MoAb. CD59 was blocked by the MoAb BRIC 229. Membrane damage of propidium iodide-stained NT2-N cells was confirmed by immunofluorescence microscopy and degeneration of neuronal processes was shown with crystal violet staining. A2B5, but not the irrelevant control IgM antibody, induced complement activation on NT2-N neurons after incubation with a human serum, as detected by the deposition of C1q. A marked membrane deposition of C5b-9 on NT2-N neurons with accompanying cell death and axonal degeneration was found after the blocking of CD59 with MoAb BRIC 229 but not with an isotype-matched control antibody. Compstatin and anti-C5 monoclonal antibodies which blocked C5 activation efficiently inhibited complement activation. In conclusion, CD59 is essential for protecting human NT2-N neurons against complement-mediated damage, which is known to occur in a number of clinical conditions including stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD59 Antigens / physiology*
  • Cell Death / immunology
  • Cell Line, Tumor
  • Cell-Free System
  • Complement Activation / immunology*
  • Complement Membrane Attack Complex / metabolism
  • Complement Membrane Attack Complex / physiology*
  • Humans
  • Immunoglobulin M / physiology
  • Neurons / immunology*
  • Neurons / metabolism
  • Neurons / pathology


  • CD59 Antigens
  • Complement Membrane Attack Complex
  • Immunoglobulin M
  • CD59 protein, human