Neonatal pattern of V-H gene utilization in nonobese diabetic mice does not correlate with development of insulitis

The nonobese diabetic (NOD) mouse model is a model of human autoimmune insu lin dependent diabetes, IDDM. The effector cells of the disease have been s hown to be T cells, but also B cells seem to contribute. Adult NOD mice hav e been shown to display a bias in their utilization of immunoglobulin (Ig) variable heavy (V-H) genes. In this study the analysis of V-H gene utilizat ion in NOD mice protected from insulitis by transgenic insertion of a major histocompatibility complex (MHC) class II E-alpha gene, point out that the bias in V-H gene expression is not correlated to disease development. The aberrant V-H gene utilization pattern in mice with the NOD genetic backgrou nd is instead suggested to be a consequence of a deregulation of the apopto sis inhibiting gene bcl-2. We also investigated if prolonged in vitro survi val of NOD lymphocytes is correlated to disease development. The E-alpha tr ansgenic NOD mice were shown to display a prolonged in vitro survival of sp leen T cells, similar to normal NOD mice. These results indicate that defec tive death mechanisms of T cells may not be primarily involved in the devel opment of autoimmune disease in these mice. However, in contrast to results from other groups, no difference in in vitro survival could be detected fo r B cells from mice with NOD genetic background compared to C57BL/6 mice.