Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus

Susceptibility to autoimmunity in B6.Sie1b mice is associated with extensive polymorphisms between two divergent haplotypes of the SLAM/CD2 family of genes. The B6.Sie1b-derived SLAM/CD2 family haplotype is found in many other laboratory mouse strains but only causes autoimmunity in the context of the C57BI/6 (136) 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.Sie1b mice. T lymphocytes from B6.Sielb 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 Ly1OB, a specific isoform of which is constitutively upregulated in B6.Sie1b lymphocytes.