The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/10/1257/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 8, October 20, 1997 1257-1267


Articles

Regulation of Anti–double-stranded DNA B Cells in Nonautoimmune Mice: Localization to the T–B Interface of the Splenic Follicle

Laura Mandik-Nayak, Anh Bui, Hooman Noorchashm, Ashlyn Eaton, and Jan Erikson

From The Wistar Institute, Philadelphia, Pennsylvania 19104

Systemic lupus erythematosus (SLE) and the MRL-lpr/lpr murine model for SLE are characterized by the presence of serum anti–double-stranded (ds)DNA antibodies (Abs), whereas nonautoimmune individuals have negligible levels of these Abs. To increase the frequency of anti-DNA B cells and identify the mechanisms involved in their regulation in nonautoimmune mice, we have used Ig transgenes (tgs). In the present study, we used the VH3H9 heavy (H) chain tg which expresses an H chain that was repeatedly isolated from anti-dsDNA Abs from MRL-lpr/lpr mice. Because the VH3H9 H chain can pair with endogenous L chains to generate anti–single-stranded DNA, anti-dsDNA, and non-DNA B cells, this allowed us to study the regulation of anti-dsDNA B cells in the context of a diverse B cell repertoire. We have identified anti-dsDNA B cells that are located at the T–B interface in the splenic follicle where they have an increased in vivo turnover rate. These anti-dsDNA B cells exhibit a unique surface phenotype suggesting developmental arrest due to antigen exposure.


Address correspondence to Dr. Jan Erikson, The Wistar Institute, Rm 273, 3601 Spruce St., Philadelphia, PA 19104. Phone: 215-898-3823; FAX: 215-573-9053; E-mail: jan{at}wista.wistar.upenn.edu

Services provided by the Wistar Institute staff were supported by the Core grant No. CA10815 and by grants from the National Institutes of Health (5R01 AI32137-06), the Arthritis Foundation, and the Pew Charitable Trust to J. Erikson. L. Mandik-Nayak is supported by the Wistar Training grant CA-09171. H. Noorchashm and A. Eaton are supported by the National Cancer Institute Training grant 2T32CA09140.

1 Abbreviations used in this paper: AP, alkaline phosphatase; BrdU, bromodeoxyuridine; ds, double-stranded; HEL, hen egg lysozyme; HRP, horseradish peroxidase; HSA, heat-stable antigen; MFI, mean fluorescence intensity; PALS, periarteriolar lymphoid sheath; ss, single-stranded; tg, transgene; V, variable.


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