The high-affinity receptor for human granulocyte/ macrophage colony-stimulating factor (hGM-CSF) is composed of two subunits, alpha and beta. The alpha-subunit binds GM-CSF with low affinity, whereas the beta-subunit does not bind GM-CSF by itself. The alpha and beta-subunits together form the high-affinity GM-CSF receptor. The beta-subunit has extensive sequence homology with the mouse interleukin 3 (IL-3) receptor (AIC2A) and its homologue (AIC2B) that does not bind IL-3 or other cytokines including GM-CSF. To examine the function of these receptor components, we expressed the alpha-subunit of the hGM-CSF receptor with the human beta-subunit or the mouse AIC2A or AIC2B in a mouse IL-3-dependent pro-B-cell line, Ba/F3, and in a mouse IL-2-dependent T-cell line, CTLL2. Coexpression of the alpha and beta-subunits in Ba/F3 and CTLL2 cells resulted in high-affinity hGM-CSF binding and growth response to low concentrations of hGM-CSF. Whereas Ba/F3 cells expressing the alpha-subunit alone proliferated in response to high concentrations of hGM-CSF, CTLL2 cells expressing the alpha-subunit alone did not respond to hGM-CSF at all. Since Ba/F3 cells express endogenous AIC2A and AIC2B whereas CTLL2 expresses neither of them, we examined the possibility that either AIC2A or AIC2B is involved in the formation of a functional GM-CSF receptor. The expression of the human alpha-subunit with AIC2B, but not with AIC2A, in CTLL2 cells conferred a growth response to hGM-CSF. These results indicate that the beta-subunit of the GM-CSF receptor is required for generation of growth signals and that AIC2B is likely the beta-subunit of the mouse GM-CSF receptor.
