Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus |
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Authors: | Wandstrat Amy E Nguyen Charles Limaye Nisha Chan Alice Y Subramanian Srividya Tian Xiang-Hong Yim Young-Sun Pertsemlidis Alexander Garner Harold R Morel Laurence Wakeland Edward K |
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Institution: | Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75235, USA. |
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Abstract: | 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. |
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