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 insulin dependent diabetes, IDDM. The effector cells of the disease have been shown to be T cells, but also B cells seem to contribute. Adult NOD mice have been shown to display a bias in their utilization of immunoglobulin (Ig) variable heavy (V(H)) genes. In this study the analysis of VH gene utilization 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 background is instead suggested to be a consequence of a deregulation of the apoptosis inhibiting gene bcl-2. We also investigated if prolonged in vitro survival of NOD lymphocytes is correlated to disease development. The E(alpha) transgenic NOD mice were shown to display a prolonged in vitro survival of spleen T cells, similar to normal NOD mice. These results indicate that defective death mechanisms of T cells may not be primarily involved in the development of autoimmune disease in these mice. However, in contrast to results from other groups, no difference in in vitro survival could be detected for B cells from mice with NOD genetic background compared to C57BL/6 mice.
Rietz
C
C
Transplantation Biology, Department of Surgery and Immunology, Mayo Clinic, Rochester, MN 55905, USA.
Screpanti
V
V
Brenden
N
N
Fernández
C
C
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002470:Cell Survival; D017931:DNA Primers / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005803:Genes, Immunoglobulin; D005802:Genes, MHC Class II; D019254:Genes, bcl-2; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic
D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region