A PRONOUNCED THYMIC B-CELL DEFICIENCY IN THE SPONTANEOUSLY DIABETIC BB RAT

In an attempt to elucidate the origin of the T cell lymphopenia and/or the beta-cell-specific autoimmunity observed in diabetes-prone Bio-Br eeding (DP-BB) rats, a thymic cDNA library was subjected to differenti al screening with thymic cDNA probes of DP-BB rats and nonlymphopenic nondiabetic controls. This approach resulted in the identification of a prominent lack of thymic B cells in DP-BB rats. This deficiency is d istinct from a less pronounced peripheral B cell deficiency of differe nt timing. The thymic B cell defect is linked to the lymphopenia trait on chromosome 4 and thereby with susceptibility to diabetes in crosse s involving the DP-BB rat, In conclusion, our data suggest that the co ntribution of thymic B cells to the (negative) selection of thymocytes is inadequate in DP-BB rats, thus providing a plausible explanation f or at least some of the spontaneous autoimmune phenomena in this anima l model.