Time course of the lymphopenia in BB rats. Relation to the onset of diabetes.

The spontaneously diabetic BB rat syndrome is associated with a marked lymphopenia, which affects all members of litters of diabetes-prone rats, and may be a necessary condition for the development of the disease. We assessed peripheral blood lymphocyte counts and subsets from birth to 66 days of age with a view to assessing the early time course. At birth, total numbers were decreased, as were total T-cells (monoclonal antibody W3/13+, with an even greater deficit in OX19+ cells), the helper/inducer subset (W3/25+), and the suppressor/cytotoxic subset (OX8+), but Ia+ (B, OX6+) cells were not reduced. There was a less-than-normal rise in these values with time, and a similar pattern was observed at 66 days. Rats followed thereafter to onset of diabetes showed no differences at 66 days that were predictive of subsequent diabetes development. Another set of rats studied at the same age and again at onset of diabetes showed no changes concurrent with diabetes onset. The data are consistent with a genetically determined defect in lymphocyte numbers that leads to a subnormal rise in circulating cells later in life, and may predispose to another unidentified factor responsible for precipitation of the beta cell cytotoxicity.