Association of Extensive Polymorphisms in the SLAM/CD2 Gene Cluster with Murine Lupus

Susceptibility to autoimmunity in B6. Sle1b mice is associated with extensive polymorphisms between two divergent haplotypes of the SLAM/CD2 family of genes. The B6. Sle1b-derived SLAM/CD2 family haplotype is found in many other laboratory mouse strains but only causes autoimmunity in the context of the C57Bl/6 (B6) genome. Phenotypic analyses have revealed variations in the structure and expression of several members of the SLAM/CD2 family in T and B lymphocytes from B6 .Sle1b mice. T lymphocytes from B6. Sle1b mice have modified signaling responses to stimulation at 4–6 weeks of age. While autoimmunity may be mediated by a combination of genes in the SLAM/CD2 family cluster, the strongest candidate is Ly108, a specific isoform of which is constitutively upregulated in B6. Sle1b lymphocytes.