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© The Rockefeller University Press, 0022-1007/1998/10/1247/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 7, October 5, 1998 1247-1254


Articles

Regulation of Anti-DNA B Cells in Recombination-activating Gene–deficient Mice

Hui Xu*, Hui Li*, Elisabeth Suri-Payer*, Richard R. Hardy{ddagger}, and Martin Weigert*

From the * Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544; and the {ddagger} 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


Address correspondence to Martin Weigert, Princeton University, Department of Molecular Biology, 401 Schultz Laboratory, Washington Rd., Princeton, NJ 08544. Phone: 609-258-4698; Fax: 609-258-2205; E-mail: mweigert{at}molbiol.princeton.edu

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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