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

• DOI: 10.1016/j.immuni.2004.10.009
• Publication Date: 2004-12-16T05:42:41Z
• Authors: Amy E. Wandstrat; Charles Nguyen; Nisha Limaye; Alice Y. Chan; Srividya Subramanian; Xiang-Hong Tian; Young-Sun Yim; Alexander Pertsem...; Harold R. Garner; Laurence Morel; Edward K. Wakeland
• Keywords: CD4-Positive T-Lymphocytes; Immunology; Molecular Sequence Data; CD2 Antigens; Immunoglobulins; Autoimmunity; Lymphocyte Activation; Mice; 03 medical and health sciences; Animals, Congenic; Antigens, CD; Immunology and Allergy; Animals; Humans; Lupus Erythematosus, Systemic; Amino Acid Sequence; Alleles; Glycoproteins; 0303 health sciences; Polymorphism, Genetic; Cell Differentiation; Infectious Diseases; Haplotypes; Multigene Family; Calcium

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.