Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus

doi:10.1084/jem.181.3.1157

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Breakdown of B cell tolerance in a mouse model of systemic lupus erythematosus

JH Roark, CL Kuntz, KA Nguyen, AJ Caton and J Erikson
Wistar Institute, Philadelphia, Pennsylvania 19104.

Anti-DNA antibodies, specifically those that stain nuclei in a homogenous nuclear (HN) fashion, are diagnostic of systemic lupus erythematosus (SLE) and the MRL-lpr/lpr SLE murine model. We have used a heavy chain transgene that increases the frequency of anti-HN antibodies to address whether their production in SLE is the consequence of a defect in B cell tolerance. Anti-HN B cells were undetectable in nonautoimmune-prone transgenic mice, but in MRL-lpr/lpr transgenic mice their Ig was evident in the sera and they were readily retrievable as hybridomas. We conclude that nonautoimmune animals actively delete anti-HN-specific B cells, and that MRL-lpr/lpr mice are defective in this process possibly because of the lpr defect in the fas gene.
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Fields, M. L., Nish, S. A., Hondowicz, B. D., Metzgar, M. H., Wharton, G. N., Caton, A. J., Erikson, J. (2005). The Influence of Effector T Cells and Fas Ligand on Lupus-Associated B Cells. J. Immunol. 175: 104-111 [Abstract] [Full Text]
Ekland, E. H., Forster, R., Lipp, M., Cyster, J. G. (2004). Requirements for Follicular Exclusion and Competitive Elimination of Autoantigen-Binding B Cells. J. Immunol. 172: 4700-4708 [Abstract] [Full Text]
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Lentz, V. M., Manser, T. (2000). Self-limiting systemic autoimmune disease during reconstitution of T cell-deficient mice with syngeneic T cells: support for a multifaceted role of T cells in the maintenance of peripheral B cell tolerance. Int Immunol 12: 1483-1497 [Abstract] [Full Text]
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Wang, H., Shlomchik, M. J. (1999). Autoantigen-specific B Cell Activation in Fas-deficient Rheumatoid Factor Immunoglobulin Transgenic Mice. J. Exp. Med. 190: 639-650 [Abstract] [Full Text]
Brard, F., Shannon, M., Prak, E. L., Litwin, S., Weigert, M. (1999). Somatic Mutation and Light Chain Rearrangement Generate Autoimmunity in Anti�single-stranded DNA Transgenic MRL/lpr Mice. J. Exp. Med. 190: 691-704 [Abstract] [Full Text]
Mandik-Nayak, L., Seo, S.-j., Sokol, C., Potts, K. M., Bui, A., Erikson, J. (1999). MRL-lpr/lpr Mice Exhibit a Defect in Maintaining Developmental Arrest and Follicular Exclusion of Anti-double-stranded DNA B Cells. J. Exp. Med. 189: 1799-1814 [Abstract] [Full Text]
Noorchashm, H., Bui, A., Li, H.-L., Eaton, A., Mandik-Nayak, L., Sokol, C., Potts, K. M., Pure, E., Erikson, J. (1999). Characterization of anergic anti-DNA B cells: B cell anergy is a T cell-independent and potentially reversible process. Int Immunol 11: 765-776 [Abstract] [Full Text]
Friedmann, D., Yachimovich, N., Mostoslavsky, G., Pewzner-Jung, Y., Ben-Yehuda, A., Rajewsky, K., Eilat, D. (1999). Production of High Affinity Autoantibodies in Autoimmune New Zealand Black/New Zealand White F1 Mice Targeted with an Anti-DNA Heavy Chain. J. Immunol. 162: 4406-4416 [Abstract] [Full Text]
Chen, Y., Stollar, B. D. (1999). DNA Binding by the VH Domain of Anti-Z-DNA Antibody and Its Modulation by Association of the VL Domain. J. Immunol. 162: 4663-4670 [Abstract] [Full Text]
Theofilopoulos, A N (1998). Effector and predisposing genes in murine lupus. Lupus 7: 575-584 [Abstract]
Kench, J. A., Russell, D. M., Nemazee, D. (1998). Efficient Peripheral Clonal Elimination of B Lymphocytes in MRL/lpr Mice Bearing Autoantibody Transgenes. J. Exp. Med. 188: 909-917 [Abstract] [Full Text]
Rathmell, J. C., Fournier, S., Weintraub, B. C., Allison, J. P., Goodnow, C. C. (1998). Repression of B7.2 on Self-reactive B Cells Is Essential to Prevent Proliferation and Allow Fas-mediated Deletion by CD4+ T Cells. J. Exp. Med. 188: 651-659 [Abstract] [Full Text]
Davidson, W. F., Giese, T., Fredrickson, T. N. (1998). Spontaneous Development of Plasmacytoid Tumors in Mice with Defective Fas-Fas Ligand Interactions. J. Exp. Med. 187: 1825-1838 [Abstract] [Full Text]
Mandik-Nayak, L., Bui, A., Noorchashm, H., Eaton, A., Erikson, J. (1997). Regulation of Anti-double-stranded DNA B Cells in Nonautoimmune Mice: Localization to the T-B Interface of the Splenic Follicle. J. Exp. Med. 186: 1257-1267 [Abstract] [Full Text]
Spatz, L., Saenko, V., Iliev, A., Jones, L., Geskin, L., Diamond, B. (1997). Light Chain Usage in Anti-double-stranded DNA B Cell Subsets: Role in Cell Fate Determination. J. Exp. Med. 185: 1317-1326 [Abstract] [Full Text]
Stollar, B.D. (1997). An overview of the anti-DNA antibody workshop: expansion of molecular structural analysis. Lupus 6: 346-348