title: Development and selection of edited B cells in B6.56R mice.
abstract: Tolerance to dsDNA is broken in mice with a high-affinity anti-DNA H chain transgene, 56R, on the C57BL/6 background (B6.56R). B6.56R produce more anti-dsDNA Abs than BALBc.56R. To investigate how anti-DNA Abs are regulated on the B6 background, phenotypic and genetic studies were performed. B6.56R have reduced numbers of B cells and phenotypically altered B cell subsets, including relative increases in the proportions of IgM-negative bone marrow B cells, cells with a marginal zone phenotype, and cells with a transitional T3 phenotype. The peripheral B cell repertoire in B6.56R is restricted: most B cells express the 56R H chain and use a similar, limited subset of editor L chains. DNA binding is more common in B6.56R because the repertoire is shifted toward L chains that are more permissive for DNA binding. H chain editing is also observed and is increased in spontaneous as compared with LPS hybridomas. A subset of spontaneous hybridomas appears to lack H chain expression.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.
authors.forename: Debora R
authors.initials: DR
authors.lastname: Sekiguchi
authors.forename: Lenka
authors.initials: L
authors.lastname: Yunk
authors.forename: David
authors.initials: D
authors.lastname: Gary
authors.forename: Deepshikha
authors.initials: D
authors.lastname: Charan
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Srivastava
authors.forename: David
authors.initials: D
authors.lastname: Allman
authors.forename: Martin G
authors.initials: MG
authors.lastname: Weigert
authors.forename: Eline T Luning
authors.initials: ET
authors.lastname: Prak
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000916:Antibody Diversity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001666:Binding Sites, Antibody; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000276:immunology; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D006825:Hybridomas; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D008070:Lipopolysaccharides / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D017393:RNA Editing; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains; D008070:Lipopolysaccharides; D004247:DNA