THY-1-MEDIATED ACTIVATION OF RAT BASOPHILIC LEUKEMIA-CELLS DOES NOT REQUIRE COEXPRESSION OF THE HIGH-AFFINITY IGE RECEPTOR

The glycosylphosphatidylinositol (GPI)-anchored protein Thy-1 is one o f the most abundant molecules expressed on the surface of rat mast cel ls and rat basophilic leukemia cells, RBL-2H3. Antibody-mediated aggre gation of Thy-1 induces in these cells release of secretory components ; so does aggregation of the receptor with high affinity for IgE (Fc e psilon RI). To examine whether there is any relationship between Thy-1 - and Fc epsilon RI-mediated activation, we have isolated from mutagen ized RBL-2H3 cells a variant cell line deficient in the expression of surface Fc epsilon RI, and analyzed its ability to be activated by an antibody to Thy-1. Northern and immuno-biot analyses revealed that the variant cells were deficient in the expression of a structural or a r egulatory gene for Fc epsilon RI gamma subunit. The cells did not resp ond by release of secretagogues and protein-tyrosine phosphorylation t o IgE and antigen and anti-Fc epsilon RI monoclonal antibody (mAb) but their response to anti-Thy-1.1 mAb and calcium ionophore A23187 was r etained. Transfection of the cloned Fc epsilon RI gamma subunit into t he variant cells restored the surface expression of Fc epsilon RI and responsiveness to both the antigen and anti-Fc epsilon RI mAb but had no effect on responsiveness to anti-Thy-1 mAb. The combined data indic ate that aggregation of surface Thy-1 glycoproteins activates a metabo lic pathway which is independent of the presence of Fc epsilon RI gamm a subunit and surface expression of Fc epsilon RI.