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Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania 19111
Anti-DNA antibodies are regulated in normal individuals but are found in high concentration in the serum of systemic lupus erythematosus (SLE) patients and the MRL lpr/lpr mouse model of SLE. We previously studied the regulation of anti–double-stranded (ds)DNA and anti–single-stranded (ss)DNA B cells in a nonautoimmune background by generating mice carrying immunoglobulin transgenes coding for anti-DNAs derived from MRL lpr/lpr. Anti-dsDNA B cells undergo receptor editing, but anti-ssDNA B cells seem to be functionally silenced. Here we have investigated how anti-DNA B cells are regulated in recombination- activating gene (RAG)-2–/– mice. In this setting, anti-dsDNA B cells are eliminated by apoptosis in the bone marrow and anti-ssDNA B cells are partially activated.
Key Words: anti-DNA antibody B cell deletion B cell anergy recombination-activating gene deficiency apoptosis
Dedicated to the memory of Eugenia Spanopoulou, whose work (described in reference 17) was the forerunner of this article.
Martin Weigert is a recipient of a National Institutes of Health grant (GM-20964-24) and Elisabeth Suri-Payer is supported by an Arthritis Investigator Award from the Arthritis Foundation.
Abbreviations used: ANA, anti-nuclear antibodies; BCR, B cell receptor; dsDNA, double-stranded DNA; RAG, recombination-activating gene; ssDNA, single-stranded DNA; tg, transgenic.
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