IL-1-BETA GENE-EXPRESSION IN B-CELLS DERIVED FROM THE MURINE MRL LPR MODEL OF LUPUS/

The MRL/lpr model of SLE resembles human lupus in its various immunopa thologic characteristics including the presence of high-level Ige and anti-DNA antibody production and multisystem organ involvement (nephri tis, arthritis, and vasculitis). Our previous studies have shown that IL-1 overactivity in B cells plays a potentially important role in dri ving IgG and autoantibody production. However, the underlying mechanis ms determining IL-1 overactivity are poorly understood. We studied IL- 1 beta gene expression and transcriptional rates in B cells derived fr om old and young MRL/lpr, MRL/+ +, and non-autoimmune control mice usi ng semi-quantitative RT-PCR and the nuclear run-on assay. RT-PCR demon strated increased steady-state IL-1 beta gene expression in B cells de rived from old MRL/lpr mice as compared to either young MRL/lpr or con trol mice. Furthermore, IL-1 beta gene expression in B cells was assoc iated with the presence of the lpr mutation because heightened IL-1 be ta message was observed in RNA obtained from MRL/lpr but not MRL/+ + B cells, IL-1 beta transcriptional rates measured by the nuclear run-on assay were very similar in B cells from old and young MRL/lpr and con trol mice. These observations suggest that IL-1 overactivity in B cell s obtained from old diseased MRL/lpr results from heightened IL-1 beta message, is associated with the presence of the lpr mutation, and is likely to reflect post-transcriptional stabilization of IL-1 beta mRNA .