Lupus-specific antiribonucleoprotein B cell tolerance in nonautoimmune mice is maintained by differentiation to B-1 and governed by B cell receptor signaling thresholds.
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.
Qian
Y
Y
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Santiago
C
C
Borrero
M
M
Tedder
T F
TF
Clarke
S H
SH
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
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