Elevated mRNA Levels of Major Histocompatibility Complex Class II Genes in Lymphocytes of Autoimmune BB Rats

The BB rat spontaneously develops autoimmune abnormalities such as insulin-dependent diabetes mellitus and thyroiditis. The autoimmunity of the BB rat is controlled in part by genes of the major histocompatibility complex (MHC), known as the RT1 complex in the rat, and accumulating evidence suggests the involvement of MHC class II molecules. The RT1 complex specifies two types of class II molecules, which are encoded by the loci RT1.B and RT1.D. We have determined the relative steady-state mRNA levels of the class II genes RTI.Bβ, RTI.Dα, and RT1.Dβ in splenic lymphocytes from individual autoimmune BB rats of various ages and from agematched histocompatible normal Wistar-Furth (WF) rats. The relative steady-state mRNA levels of the RTI.Dα and RT1.Dβ genes, but not of the RT1.Bβ gene, were elevated ∼2.5-fold in lymphocytes of prediabetic BB rats 45–75 days old in comparison with age-matched normal WF rats and older BB rats >75 days old. In the diabetic and nondiabetic BB rats >75 days old, the RTI.Dα and RT1.Dβ transcripts were found at lower normal levels, similar to that of WF rats. In contrast, the RTI.Bβ transcripts were found at comparable levels in lymphocytes of the BB and WF rats at all ages examined. The increased steady-state mRNA levels of the RTI.Dα and RTI.Dβ genes in the prediabetic BB rats may reflect differences in the proportion of lymphocytes expressing these genes and thus differences in splenic lymphocyte populations. These elevated steady-state mRNA levels of both RT1.D genes in lymphocytes of prediabetic BB rats correlate with the age when the autoimmune effector mechanisms are highly activated and suggest an involvement of RT1.D class II antigens with the autoimmune disease process in the BB rat. The differences in steady-state class II mRNA levels in prediabetic BB rats and the age-matched normal WF rats and older BB rats suggest that the RTI.Dα and RTI.Dβ genes are similarly regulated, but not coordinately regulated with the RTI.Bβ gene, in splenic lymphocytes of young autoimmune BB rats.