Protein Kinase C Expression Links Natural Antibody Binding with Surveillance of Activated and Preneoplastic Cells

Extensive evidence supports a role for natural antibody (NAb) acting against small tumour foci in vivo . Ras‐transformation of murine C3H 10T½ fibroblasts, known to partially activate and down‐regulate endogenous PKC‐α, increased their serum NAb‐binding capacity consistent with the requirements for natural immune surveillance. Now a rat PKC‐β1‐overexpressing 10T½ clone, PKC‐4, with an 11‐fold increase in PKC activity and an activated, partially transformed phenotype, links higher susceptibility to transformation through v‐Ha‐ras infection with an 80% increase in NAb binding assayed by flow cytometry. H7 and E‐64d inhibition and phorbol ester depletion of PKC reduced NAb binding. PKC‐β1 expression and NAb binding exhibited a similar temporal recovery from TPA treatment. Thus, expression of NAb‐binding structures appears to be elevated by constitutive increases in the basal activation of PKC in both the ras‐transformation and the PKC‐β1‐preneoplasia models. This, coupled with corresponding decreases in membrane PKC‐α and NAb binding in confluent 10T½ cells raises the possibility that in general, cells activated through PKC are NAb sensitive. Together with the increased in vivo elimination of the high NAb‐binding PKC‐4 cells, the data extend the support for a role for NAb in immune surveillance, to resistance against preneoplastic cells, and argue for NAb contributing to homeostasis of the organism.