Possible role of tyrosine kinase activity in interleukin 4–induced expression of germ-line Cϵ transcripts in a human Burkitt lymphoma B-cell line, DND39

Abstract

Despite the recent advances in knowledge of the molecular mechanism by which interleukin-4 (IL-4) induces IgE production, little is known about the signal transduction pathway that leads to this event. This study investigated the signal transduction mechanism responsible for IL-4–induced expression of germ-line Cϵ transcripts with use of a human Burkitt lymphoma B-cell line, DND39, which is known to express germ-line Cϵ transcripts in response to IL-4. On stimulation with IL-4, the generation of inositol triphosphate was observed in the cells. In addition, this generation was associated with activation of phospholipase C-γ1 (PLC-γ1). Although herbimycin A, a potent inhibitor of tryosine kinase, inhibited IL-4–induced activation of PLC-γ1 and generation of inositol triphosphate, direct phosphorylation of PCL-γ1 was not determined. Nevertheless, IL-4 stimulation could induce activation of FYN but not LYN kinase, suggesting that additional molecule(s) might link FYN kinase to PLC-γ1. Interestingly, herbimycin A almost completely inhibited IL-4–induced expression of germ-line Cϵ transcripts when present during the entire culture period. These results indicate that the induction of germ-line Cϵ transcripts in IL-4–stimulated DND39 cells is essentially dependent on the activation of tyrosine kinase, possibly FYN kinase. (J ALLERGY CLIN IMMUNOL 1994;94:620-4.)