The "early birds": natural IgM antibodies and immune surveillance

Precancerous epithelial lesions are sites of uncontrolled cellular proliferation generated by irreversible genetic alterations. Not all of those lesions progress to invasive cancer, some may even regress, but the early detection of abnormal cells can be crucial for patient survival. Immune surveillance mechanisms are responsible for the removal of transformed cells and antibodies play an important role in these immune processes. In the past, analysis of the immunoglobuline repertoire has focused mainly on xenoimmunizations or the investigation of cancer patient immunity. The human hybridoma technology (Trioma technique) offers the unique possibility to study the humoral immunity of healthy people. Using this technique a series of tumor-binding antibodies could be isolated which all have several features in common: they are germ-line coded IgM antibodies, they predominantly bind to carbohydrates on post-transcriptionally modified antigens, they induce apoptosis and, most importantly, they detect not only malignant cells but also precursor stages. These data demonstrate that the body has a comprehensive defense system against malignant cells based on the production of natural antibodies.