INTERLEUKIN-6: A TRANSCRIPTION ACTIVATING CYTOKINE

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Interleukin-6 (IL-6), a 20-26 kDa phospho-glycoprotein whose gene has been cloned and sequenced in a variety of heterologous systems, has been reported to induce Ig secretion in activated B cells, acting as a growth and differentiation factor for these cells. Because both the Ig genes and their regulatory elements have been characterized in detail, study of the molecular mechanisms governing Ig secretion induced by IL-6 provides an ideal model system for investigation. Recently, IL-6 was reported to transcriptionally activate gamma1 heavy chain and gamma light chain genes in a subclone of the lymphoblastoid cell line CESS that was selected on the basis of high density IgG1 surface expression. The purpose of the present study was to investigate further the molecular basis for Ig production induced by IL-6. Using a panel of B cell lines obtained by EBV immortalization of normal human B lymphocytes, we confirmed that IL-6 stimulates Ig gene transcription, causing significant increases in the amounts of mRNA per cell. We further showed that IL-6 induces expression of the growth responsive genes c-myc and actin, followed by increases in DNA, RNA and protein synthesis as well as cell numbers. Thus, IL-6 does not selectively activate Ig transcription but acts as a B cell stimulatory factor transcriptionally activating several growth responsive genes.