Abstract
The degree of heavy chain (H) editing, the types of Vkappa editors, and the pattern of Jkappa usage are correlated with a range of the affinity of anti-DNA. This range was determined by the number and location of arginine (R) residues in the VH. We, here, changed a key arginine residue in the VH of anti-DNA transgene to glycine, which sharply reduces the affinity for dsDNA. However, complete reversion of this anti-DNA to germline enhances the affinity for phosphatidylserine (PS). The B cells of this low-affinity anti-DNA and anti-PS transgenic mouse are tightly regulated by receptor editing. Thus, anti-PS B cells are another example of a constitutive self-antigen regulated in the bone marrow.
MeSH terms
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Animals
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Animals, Congenic
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Antibodies, Antiphospholipid / chemistry
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Antibodies, Antiphospholipid / genetics*
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Antibodies, Antiphospholipid / metabolism
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Autoantigens
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DNA / metabolism
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Gene Rearrangement, B-Lymphocyte, Heavy Chain
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Gene Rearrangement, B-Lymphocyte, Light Chain
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Hybridomas / immunology
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Immunoglobulin Heavy Chains / chemistry
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Immunoglobulin Heavy Chains / genetics
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Immunoglobulin Heavy Chains / metabolism
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Immunoglobulin kappa-Chains / chemistry
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Immunoglobulin kappa-Chains / genetics
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Immunoglobulin kappa-Chains / metabolism
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Mice
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Mice, Inbred BALB C
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Mice, Transgenic
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Models, Molecular
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Mutagenesis, Site-Directed
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Phosphatidylserines / immunology*
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RNA Editing
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Self Tolerance
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Static Electricity
Substances
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Antibodies, Antiphospholipid
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Autoantigens
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Immunoglobulin Heavy Chains
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Immunoglobulin kappa-Chains
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Phosphatidylserines
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DNA