Autoreactive B cell regulation: peripheral induction of developmental arrest by lupus-associated autoantigens.
Anti-Sm and anti-ssDNA transgenic (Tg) mice were generated using the VH-D-JH rearrangement of an anti-Sm hybridoma of MRL/Mp-lpr/lpr origin. B cells of each specificity account for 15%-35% of the splenic repertoire, but no circulating anti-Sm or anti-ssDNA antibodies are detected. Most autoreactive cells exhibit an immature B cell phenotype and have short half-lives equivalent to those of non-Tg immature B cells. However, at least some anti-Sm B cells are functional, because immunization with murine snRNPs induces anti-Sm secretion. We propose that anti-Sm and anti-ssDNA are eliminated during the transition to mature B cells and that this late stage of tolerance induction is consequential to their spontaneous activation in murine lupus.
Santulli-Marotto
S
S
Department of Microbiology and Immunology, University of North Carolina, Chapel Hill 27599, USA.
Retter
M W
MW
Gee
R
R
Mamula
M J
MJ
Clarke
S H
SH
D000818:Animals; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D004277:DNA, Single-Stranded / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006412:Hematopoietic Stem Cells; D006825:Hybridomas; D007108:Immune Tolerance; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology; D013154:Spleen / Q000276:immunology; D055517:snRNP Core Proteins
D001324:Autoantigens; D004277:DNA, Single-Stranded; D017411:Ribonucleoproteins, Small Nuclear; C526416:Snrpb protein, mouse; D055517:snRNP Core Proteins