Normal human serum contains a natural IgM antibody cytotoxic for human neuroblastoma cells

Markus W. Ollert, Kerstin David, Caroline Schmitt, Alexander Hauenschild*, Reinhard Bredehorst, Rudolf Erttmann, Carl Wilhelm Vogel

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

62 Citations (Scopus)


Neuroblastoma (NB) is characterized by the second highest spontaneous regression of any human malignant disorder, a phenomenon that remains to be elucidated. In this study, a survey of 94 normal human adult sera revealed a considerable natural humoral cytotoxicity against human NB cell lines in approximately one-third of the tested sera of both genders. Specific cell killing by these sera was in the range of 40% to 95%. Serum cytotoxicity was dependent on an intact classical pathway of complement. By several lines of evidence, IgM antibodies were identified as the cytotoxic factor in the sera. Further analyses revealed that a 260-kDa protein was recognized by natural IgM of cytotoxic sera in Western blots of NB cell extracts. The antigen was expressed on the surface of seven human NB cell lines but not on human melanoma or other control tumor cell lines derived from kidney, pancreas, colon, bone, skeletal muscle, lymphatic system, and bone marrow. Furthermore, no reactivity was observed with normal human fibroblasts, melanocytes, and epidermal keratinocytes. The antigen was expressed in vivo as detected by immunohistochemistry in both the tumor of a NB patient and NB tumors established in nude rats from human NB cell lines. Most interestingly, the IgM anti-NB antibody was absent from the sera of 11 human NB patients with active disease. The anti-NB IgM also could not be detected in tumor tissue obtained from a NB patient. Collectively, our data suggest the existence of a natural humoral immunological tumor defense mechanism, which could account for the in vivo phenomenon of spontaneous NB tumor regression.

Original languageEnglish
Pages (from-to)4498-4503
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
Publication statusPublished - 30 Apr 1996
Externally publishedYes


  • minor antibody
  • natural immunity
  • tumor antigen


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