EXPRESSION OF 2 INTERLEUKIN-4 MESSENGER-RNA ISOFORMS IN B-LYMPHOID-CELLS

Expression of an alternative spliced IL4 mRNA was found in in vibro ac tivated T cells. In this study we show that the expression of IL4 mRNA , as well as the expression of this alternatively spliced form of IL4 mRNA, is not restricted to these cells. We analyzed different human ly mphoid tissues and cell lines of different origin and found that the a lternatively spliced IL4 transcripts are also expressed in human lymph oid tissues, in purified B cells, in the various B cell-derived cell l ines, and even in nonlymphoid cell lines. Stimulation with the phorbol ester PMA enhanced expression of both transcripts in all cells studie d. The two IL4 transcripts were cloned and sequenced from the B cell l ine Namalwa. In the alternatively spliced form, the same exon 2 is del eted as has been observed in in vitro activated T cells. In principle, such alternatively spliced mRNA may give rise to a truncated IL4 prot ein, as the deletion does not result in a frameshift. We tested supern atants of activated PBMC, cell lines, and cell extracts for the presen ce of IL4 protein. We found IL4 protein expression in activated PBMC, but not in any of the stimulated cell lines or in the purified B cells . Using a modified in situ hybridization method with Dig-labeled PCR p roducts, however, these cells did express IL4 mRNA. This shows that tr anscription of both IL4 forms is not restricted to T cells and can be induced in other cell types as well. Using these non-T cells, no prote in has been found in the supernatant, however. It is possible that tra nscription of the IL4 gene is not necessarily followed by translation and that translation into the IL4 protein requires an additional signa l. (C) 1996 Academic Press, Inc.