Abstract
Circulating human B cells that coexpress V-preB and conventional L chains (V-preB+L+ B cells) are a recently described subset of B cells that express Abs with features of self-reactivity. Initial analysis of V-preB+L+ B cells was limited to Ig-kappa and to the small, underused VH5 family. To determine whether Abs commonly expressed by V-preB+L+ B cells show similar features, we analyzed Ig H chains from three highly expressed VH families, VH1, VH3, and VH4, and Ig-lambda. We find that VH1 and VH3 Abs expressed by V-preB+L+ B cells resemble VH5 in that they display increased JH6 use, long CDR3s, and an increased frequency of D-D fusions. Abs in all three of these VH families also show skewed D reading frame use resulting in predominance of hydrophobic amino acids, which are counterselected in conventional B cells. Like Ig-kappa genes, the Ig-lambda genes in V-preB+L+ B cells show long CDR3s, but they differ from Ig-kappa genes in that they display no evidence of receptor editing. We conclude that a large number of H and L chain Abs expressed by V-preB+L+ B cells display features associated with self-reactive Abs.
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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Antibody Diversity* / genetics
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism*
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Complementarity Determining Regions / biosynthesis
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Complementarity Determining Regions / blood
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Gene Rearrangement, B-Lymphocyte, Heavy Chain
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Gene Rearrangement, B-Lymphocyte, Light Chain
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Humans
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Immunoglobulin Heavy Chains / biosynthesis
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Immunoglobulin Heavy Chains / blood
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Immunoglobulin Light Chains / biosynthesis*
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Immunoglobulin Light Chains / blood
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Immunoglobulin Light Chains / genetics
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Immunoglobulin Light Chains, Surrogate
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Immunoglobulin Variable Region / biosynthesis
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Immunoglobulin Variable Region / blood
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Immunoglobulin Variable Region / genetics
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Immunoglobulin kappa-Chains / biosynthesis
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Immunoglobulin kappa-Chains / blood
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Immunoglobulin lambda-Chains / biosynthesis
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Immunoglobulin lambda-Chains / blood
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / blood
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Membrane Glycoproteins / genetics
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Stem Cells / immunology
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Stem Cells / metabolism
Substances
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Complementarity Determining Regions
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Immunoglobulin Heavy Chains
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Immunoglobulin Light Chains
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Immunoglobulin Light Chains, Surrogate
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Immunoglobulin Variable Region
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Immunoglobulin kappa-Chains
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Immunoglobulin lambda-Chains
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Membrane Glycoproteins