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Certain Burkitt´s B lymphoma cells have a high number of receptors for interelukin-4 (IL-4), yet appear less sensitive to the biological effect of IL-4 than normal resting B-cells. Since receptor modulation is an important event for the effective signal transduction by the respective ligand, we have investigated the expression and modulation of the IL-4 receptor (IL-4R) in normal vs. transformed B-cells upon treatment with IL-4 and other B-cell activators. Normal tonsillar B-cells showed a low level of IL-4R gene expression in the resting stage, which can be rapidly up-regulated by treatment with IL-4, anti-CD40, or PMA. By contrast, a Burkitt´s lymphoma cell line, Raji, displayed a high basal expression of IL-4R mRNA and no apparent modulation of the receptor expression by IL-4, anti-CD40 antibody (anti-CD40), or PMA. A noticeable induction of CD23 gene expression by IL-4 was concomitantly observed in normal B-cells, but not in Raju cells. We also observed that in the case of normal B-cells, IL-4 and anti-CD40 acted at least in an additive manner to induce up-regulation of IL-4R. Thus, IL-4R up-regulation appears important for an effective IL-4 response, such as CD23 induction, to occur, and for the delivery of CD40-mediated signal, which induces B-cell activation cooperatively with IL-4, probably by amplifying the IL-4-induced signal. The analysis of the subunit structure of IL-4R by immunoprecipitation and Western blot using anti-IL-4R mAbs revealed distinct peptides of a 110 kDa and a 140 kDa in normal B-cells and Raji cells, respectively, each of which was phosphorylated by an IL-4R-associated kinase. Taken together, these results suggest that differential gene expression and modulation of the IL-4R as well as a distinct subunit structure of the receptor may in part constitute the biochemical basis of differential IL-4 response and signal transduction in normal and transformed B-cells.
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