Fluorescence-activated cell sorting was used to isolate high and low IgM natural antibody (NAb) binding populations from a heterogeneous line of the L5178Y-F9 murine lymphoma. The ranking of NAb binding and complement-dependent NAb lysis of the selected and starting lines were the same and opposite to that of their tumorigenicity in syngeneic DBA/2 mice. L5178Y-F9 and SL2-5 clones repeatedly treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate and selected by fluorescence-activated cell sorting for high NAb binding exhibited increases in NAb binding and sensitivity to complement-dependent NAb lysis which corresponded with reduced tumor frequencies of threshold inocula. Although the high NAb binding SL2-5 line was slightly more sensitive to natural killer (NK) cell cytolysis, changes in susceptibility to activated macrophages or hypotonic lysis were not consistent with the observed reductions in tumor frequency so that the selected alterations in NAb binding corresponded best with tumorigenicity. These data confirm the same inverse relationship exhibited previously by in vivo and in vitro selected tumor variants and provide more precise evidence supporting a role for NAb in host resistance against tumor foci.

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Supported by the Medical Research Council of Canada. Animals were maintained under guidelines set forth by the University of Manitoba.

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