The effects of interleukin 4 on the cell cycle of a human B‐cell lymphoma line

Abstract. Exposure of Farage, a human B‐cell lymphoma line, to IL‐4 for 3–11 days led to inhibition of tritiated thymidine ([³H]dT) uptake by the cells. Study of the incorporation of 5‐bromodeoxyuridine by Farage cells showed that IL‐4 reduced significantly the number of cells in the S phase of the cell cycle and increased the proportion of cells in the G₁ phase. Limiting dilution analysis of proliferation demonstrated that IL‐4 decreased the frequency of clone‐forming cells by 40%. IL‐4 did not reduce the viability of Farage cells. On the contrary, IL‐4 diminished the spontaneous death of Farage cells in culture, as determined by pulse chase analysis of cells which were labelled with [³H]dT. Moreover, the pre‐treatment of Farage cells with IL‐4 prevented their death induced by exposure to a high dose of staurosporine. IL‐4 abrogated the staurosporine‐induced arrest of cells in the G₂+ M phase and replaced it by accumulation of cells in the G₁ phase. IL‐4 protected Farage cells from the radioactive suicide caused by the uptake of [³H]dT by dividing cells. The cytokine failed to prevent the damage to Farage cells exerted by mitomycin C, which affected cellular DNA regardless of the phase of the cell cycle. The data obtained showed that IL‐4 inhibited the division of B cells by arresting their progression through the early stages of the cell cycle. This inhibition of the cell efflux from G₁ phase plays an important role in the protection against cell death during further stages of the cell cycle.