Natural IgM antibodies and immunosurveillance mechanisms against epithelial cancer cells in humans.

Malignancy is like a chronic disease, and the immune system is permanently involved in recognizing and eliminating the transformed cells. The human hybridoma technology offers the unique opportunity to study the mechanisms, structures, and targets involved in recognition and elimination of aberrant cells. Thousands of tumor-reactive human monoclonal antibodies were isolated by this technique from cancer patients and from healthy donors, and all of these antibodies were IgM antibodies; no IgG and IgA antibodies were found. Fourteen of these antibodies were selected for DNA sequence analysis, characterization of their binding patterns, and determination of their origin and genetics. All of the IgM antibodies studied expressed only few or no mutations at all (germ-line coded), bound to carbohydrates on modified tumor-specific receptors and induced apoptosis. The degree of cross-reactivity to other tumors correlated reciprocally with the number of mutations in coding regions. By using an anti-idiotypic antibody we were able to show that the IgM-producing cells were of CD5+ B-cell origin. The data presented here indicate that the innate immunity and natural IgM antibodies play an important role in immunosurveillance mechanisms against epithelial tumors in humans.