title: Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds.
abstract: Systemic lupus erythematosus is an autoimmune disease characterized by the presence of autoantibodies. One of the unique targets of the immune system in systemic lupus erythematosus is Sm, a ribonucleoprotein present in all cells. To understand the regulation of B cells specific to the Sm Ag in normal mice, we have generated an Ig H chain transgenic mouse (2-12H Tg). 2-12H Tg mice produce B cells specific for the Sm that remain tolerant due to ignorance. We demonstrate here that anti-Sm B cells of 2-12H Tg mice can differentiate into Sm-specific peritoneal B-1 cells that remain tolerant. Differentiation to B-1 and tolerance are governed by the strength of B cell receptor signaling, since manipulations of the B cell receptor coreceptors CD19 and CD22 affect anti-Sm B cell differentiation and autoantibody production. These results suggest a differentiation scheme in which peripheral ignorance to Sm is maintained in mice by the differentiation of anti-Sm B cells to B-1 cells that have increased activation thresholds.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Qian
authors.forename: C
authors.initials: C
authors.lastname: Santiago
authors.forename: M
authors.initials: M
authors.lastname: Borrero
authors.forename: T F
authors.initials: TF
authors.lastname: Tedder
authors.forename: S H
authors.initials: SH
authors.lastname: Clarke
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D018941:Antigens, CD19 / Q000096:biosynthesis / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001323:Autoantibodies / Q000097:blood / Q000502:physiology; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D007108:Immune Tolerance / Q000235:genetics; D037102:Lectins; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010537:Peritoneum / Q000166:cytology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis / Q000502:physiology*; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D055517:snRNP Core Proteins
chemical_list: D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D001323:Autoantibodies; D001324:Autoantigens; C497868:Cd22 protein, mouse; D015815:Cell Adhesion Molecules; D037102:Lectins; D011947:Receptors, Antigen, B-Cell; D017411:Ribonucleoproteins, Small Nuclear; D051918:Sialic Acid Binding Ig-like Lectin 2; C526416:Snrpb protein, mouse; D055517:snRNP Core Proteins