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The expression of 4-1BB has been known to be depend-ent on T cell activation. Recent studies , however, have, however, reve-aled that 4-1BB expression is not restricted to T cells. We sought to determine the molecular basis for the differential gene expression. Here we report that the expression pattern of two mouse 4-1BB transcripts, has three full-length transcripts named type I and, type II. Whereas the type I transcript was specifically expressed on immune organ as previously reported, the type II transcript was ubiquitously expressed in tissues and various cell lines. However, both type I and type II transcript were highly induced on activated T cells., and type IIII, that show different expression patterns. Primer extension assay of the two 4-1BB transcripts suggested that mouse 4-1BB had more than two transcripts. Previously, type I and type II were identified and additional type III transcript, which has no 1 exons, was found. Using luciferase assay we have identified three promoterpromoter regions (PI, PII and PIII) in the mouse 4-1BB gene, which located on up-stream region of second exon 1, first exon 1, and exon 2, respectively.. ified an upstream region of the type I and type III transcripts that has promoter activity. The expres-sion of the three 4-1BB transcripts was investigated in naive T cells and EL4 cell lines. Whereas the type III tran-script was highly induced on activated T cells as previously reported, the type II transcript was ubiquitously expressedd in tissues and various cell lines. In particular, the type I transcript was preferentially induced whenin naive T cells are stimu-lated by anti-CD3 monoclonal antibody (mAb) since NF-κB specifically binds to the putative NF-κB element of an upstream region of the type I transcriptPI. This suggests that the upstream region of the type I transcript is responsible for activation-induced expression of 4-1BB in naive T cells. We have also shown that a splice variant, in which exon 8 (including the transmembrane domain) was deleted, and which could inhibit 4-1BB signaling. The splicing variant was, was highly induced by TCR stimulation. Our results reveal 4-1BB has three transcripts, and the proximal region of the type I transcript is an inducible promoter in naive T cells. 4-1BB also has a negative regulation system through soluble 4-1BB produced from a splice variant induced under activation conditions.
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