Bcl-2 leads to expression of anti-DNA B cells but no nephritis: a model for a clinical subset.
Transgenic mice expressing anti-DNA antibodies have been extensively studied as a model for understanding B cell regulation in systemic lupus erythematosus (SLE). BALB/c mice transgenic for the R4A-gamma2b heavy chain of an anti-double-stranded DNA (dsDNA) antibody produce two populations of high-affinity anti-dsDNA B cells, one deleted, and the other anergized. We generated double-transgenic BALB / c mice expressing both the R4A-gamma2b heavy chain and the anti-apoptotic bcl-2 gene in the B cell compartment to study whether bcl-2 overexpression differentially affected anergic and deleted B cells. The double-transgenic mice (R4A/bcl-2) express elevated serum titers of both high- and low-affinity anti-dsDNA antibodies and display rescue of autoreactive B cells that are normally either deleted or anergized. Despite the presence of anti-dsDNA antibodies in their serum, R4A/bcl-2-transgenic mice do not develop nephritis, demonstrating that overexpression of bcl-2 is not by itself sufficient to allow disease progression. This phenotype resembles that of some SLE patients who have high titers of anti-DNA antibodies without nephritis.
Kuo
P
P
Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York 10461, USA.
Bynoe
M S
MS
Wang
C
C
Diamond
B
B
D000595:Amino Acid Sequence; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D000915:Antibody Affinity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D004195:Disease Models, Animal; D005803:Genes, Immunoglobulin; D006825:Hybridomas / Q000276:immunology / Q000378:metabolism; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009393:Nephritis / Q000209:etiology / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D013154:Spleen / Q000276:immunology
D000974:Antibodies, Antinuclear; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D019253:Proto-Oncogene Proteins c-bcl-2