Circulating human B cells that express surrogate light chains display a unique antibody repertoire.
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.
Meffre
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E
Laboratory of Molecular Immunology, and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
Chiorazzi
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Nussenzweig
M C
MC
D000916:Antibody Diversity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D022801:Complementarity Determining Regions / Q000096:biosynthesis / Q000097:blood; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000097:blood; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000096:biosynthesis / Q000097:blood; D007146:Immunoglobulin lambda-Chains / Q000096:biosynthesis / Q000097:blood; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism
D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains; D008562:Membrane Glycoproteins