Polyclonal natural antitumor antibody binding dynamics: preferential release of surface membrane molecules and increased metastasis.
Flow cytometry revealed the dynamic nature of polyclonal whole serum naturally occurring IgG and IgM antibody binding to the syngeneic murine T cell lymphomas SL2-5, L5178Y-F9 and the in vitro selected high natural antibody binding variant L5178Y-F9 TPA/NAb+3. This was particularly evident at physiological conditions where the temperature was 37 degrees C and the concentration of reactive serum natural antibodies (NAb) was high. Lower binding was observed at 37 versus 4 degrees C, or after raising the temperature from 4 to 37 degrees C, a procedure which was associated with an augmented loss of 125I-surface-labelled material from cells incubated in NAb compared to cells exposed to growth media. Even at 4 degrees C, NAb binding exhibited biphasic kinetics suggesting a loss of surface-bound NAb and a subsequent cycle of NAb uptake. The increased intravenous liver metastasis potential of the high NAb binding L5178Y-F9 TPA/NAb+3 corresponded with its higher total loss of 125I-surface-labelled material when incubated in NAb at 37 degrees C, and with its extensive loss of NAb binding when the temperature was raised from 4 to 37 degrees C. These observations are consistent with the idea that molecules released from the cell may contribute to the higher metastasis. This thinking was supported by the increased metastasis of tumor cells injected intravenously, either with serum in which they had been preincubated at 37 degrees C or into mice treated with supernatants from tumor cells incubated in NAb.
Chow
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Department of Immunology, University of Manitoba, Winnipeg, Canada.
Yuan
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Tough
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D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism*; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D001666:Binding Sites, Antibody; D002462:Cell Membrane / Q000378:metabolism; D005434:Flow Cytometry; D007457:Iodine Radioisotopes; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D016399:Lymphoma, T-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D009362:Neoplasm Metastasis; D011402:Pronase / Q000494:pharmacology; D013696:Temperature; D014407:Tumor Cells, Cultured
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007457:Iodine Radioisotopes; D011402:Pronase