Editors and editing of anti-DNA receptors.
Receptor editing is a means by which immature bone marrow B cells can become self-tolerant. Rearrangements of heavy (H) and/or light (L) chain genes are induced by encounter with autoantigens to change the specificity from self to nonself. We have developed site-directed transgenic mice (sd-tg) whose transgenes code for the H chain of antibodies that bind DNA. B cells that express the transgenic H chain associate mainly with four of the 93 functional Vkappa genes of the mouse. Numerous aspartate residues that might inhibit DNA binding by the V(H) domain distinguish these L chain Vkappa sequences, but engaging these Vkappa editors often requires multiple rearrangements. Among the edited B cells is a subset of multispecific cells that express multiple receptors. One consequence of multispecificity is partial autoreactivity; these multispecific B cells may contribute to autoimmunity.
Li
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Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Jiang
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Y
Prak
E L
EL
Radic
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Weigert
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M
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000974:Antibodies, Antinuclear / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D003062:Codon / Q000235:genetics; D004247:DNA / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007526:Isoelectric Point; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D017634:Self Tolerance / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019076:Transgenes
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001324:Autoantigens; D003062:Codon; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D004247:DNA