Interferon-γ receptor 2 expression as the deciding factor in human T, B, and myeloid cell proliferation or death

Theheterodimeric interferon (IFN)‐γ receptor (IFN‐γR) is formed of two chains. Here we show that the binding chain (IFN‐γR1) was highly expressed on the membranes of T, B, and myeloid cells. Conversely, the transducing chain (IFN‐γR2) was highly expressed on the surfaces of myeloid cells, moderately expressed on B cells, and poorly expressed on the surfaces of T cells. Differential cell membrane expression of IFN‐γR2 determined the number of receptor complexes that transduced the IFN‐γ signal and resulted in a different response to IFN‐γ. After IFN‐γ stimulation, high IFN‐γR2 membrane expression induced rapid activation of signal transducer and activator of transcription‐1 (STAT‐1) and high levels of interferon regulatory factor‐1 (IRF‐1), which then triggered the apoptotic program. By contrast, low cell membrane expression resulted in slow activation of STAT‐1, lower levels of IRF‐1, and induction of proliferation. Because the forced expression of IFN‐γR2 on T cells switched their response to IFN‐γ from proliferative to apoptotic, we concluded that the surface expression of IFN‐γR2 determines whether a cell stimulated by IFN‐γ undergoes proliferation or apoptosis.