B cell selection and allelic exclusion of an anti-DNA Ig transgene in MRL-lpr/lpr mice.
We have used an Ig transgene (VH3H9) that increases the frequency of anti-DNA autoantibodies to address whether the production of antinuclear Abs in systemic lupus erythematosus is the consequence of a breakdown of B cell tolerance. We have shown that nonautoimmune mice regulate anti-DNA B cells, and that lupus-prone MRL-lpr/lpr mice are defective in this regulation. Here we show that a subset of anti-DNA B cells, namely those that stain nuclei in a homogeneous fashion, not only fail to be deleted in MRL-lpr/lpr mice, but undergo preferential clonal expansion. In addition, we describe a surprising finding: the VH3H9 transgene is less efficient at inhibiting endogenous heavy chain gene rearrangement on the autoimmune-prone MRL-lpr/lpr genetic background than on the nonautoimmune BALB/c background.
Roark
J H
JH
Wistar Institute, Philadelphia, PA 19104, USA.
Kuntz
C L
CL
Nguyen
K A
KA
Mandik
L
L
Cattermole
M
M
Erikson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000235:genetics*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D005786:Gene Expression Regulation / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007126:Immunoglobulin Allotypes / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008969:Molecular Sequence Data
D000974:Antibodies, Antinuclear; D007126:Immunoglobulin Allotypes; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007147:Immunoglobulin Light Chains