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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Amino Acid Sequence
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Animals
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Animals, Congenic
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Antigens, CD
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Autoimmunity / genetics
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Autoimmunity / immunology
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CD2 Antigens / chemistry
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CD2 Antigens / genetics*
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CD2 Antigens / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / pathology
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Calcium / metabolism
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Cell Differentiation
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Glycoproteins / chemistry
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Glycoproteins / genetics*
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Glycoproteins / immunology
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Haplotypes / genetics
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Humans
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Immunoglobulins / chemistry
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Immunoglobulins / genetics*
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Immunoglobulins / immunology
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Lupus Erythematosus, Systemic / genetics*
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Lupus Erythematosus, Systemic / immunology
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Lupus Erythematosus, Systemic / metabolism
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Lupus Erythematosus, Systemic / pathology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mice
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Molecular Sequence Data
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Multigene Family / genetics*
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Polymorphism, Genetic / genetics*
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Receptors, Cell Surface
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Sequence Analysis, DNA
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Signaling Lymphocytic Activation Molecule Family
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Signaling Lymphocytic Activation Molecule Family Member 1
Substances
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Antigens, CD
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CD2 Antigens
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Glycoproteins
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Immunoglobulins
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Receptors, Cell Surface
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SLAMF6 protein, human
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Signaling Lymphocytic Activation Molecule Family
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Slamf6 protein, mouse
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Signaling Lymphocytic Activation Molecule Family Member 1
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Calcium