Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus.
Anti-DNA antibodies, specifically those that stain nuclei in a homogenous nuclear (HN) fashion, are diagnostic of systemic lupus erythematosus (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy chain transgene that increases the frequency of anti-HN antibodies to address whether their production in SLE is the consequence of a defect in B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune-prone transgenic mice, but in MRL-lpr/lpr transgenic mice their Ig was evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specific B cells, and that MRL-lpr/lpr mice are defective in this process possibly because of the lpr defect in the fas gene.
Roark
J H
JH
Wistar Institute, Philadelphia, Pennsylvania 19104.
Kuntz
C L
CL
Nguyen
K A
KA
Caton
A J
AJ
Erikson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000954:Antigens, Surface / Q000235:genetics / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D004277:DNA, Single-Stranded / Q000276:immunology; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000276:immunology; D007108:Immune Tolerance; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D019014:fas Receptor
D000974:Antibodies, Antinuclear; D000954:Antigens, Surface; D004277:DNA, Single-Stranded; D007135:Immunoglobulin Variable Region; D019014:fas Receptor