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The site and stage of anti-DNA B-cell deletion

Nature volume 373, pages 252–255 (1995)Cite this article

Abstract

ANTIBODIES to DNA and nucleoproteins are found in sera of individuals with systemic autoimmune disease. In the population (and in the autoimmune mouse strain MRL/lpr) there is a great variety of such antinuclear antibodies, but individuals with systemic lupus erythematosus or single MRL mice express a subset only of the antinuclear specificities found in the population. These observations have been interpreted to mean that these antibodies arise by immunization1. The oligoclonal nature of the autoantibody response and the evidence of selection acting on somatically mutated autoantibodies favour this interpretation2,3. Specific activation of autoantibodies in disease implies either that autoantibodies are regulated in non-diseased individuals or that autoantigen availability is variable. The former has been demonstrated in anti-DNA transgenic mice. In normal mice, transgene-encoded antibodies against double-stranded (ds) DNA are not expressed in serum or on B cells4–6. Here we describe modified anti-dsDNA transgenic mice which allow us to study the site and developmental stage at which such B-cell regulation occurs. This model shows that in normal mice B cells expressing anti-DNA specificity are deleted in the bone marrow at a pre-B to immature B transitional stage.

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Authors and Affiliations

  1. Department of Molecular Biology, Princeton University, Princeton, New Jersey, 08544, USA

    Ching Chen & Zoltan Nagy

  2. Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia, Pennsylvania, 19129, USA

    Marko Z. Radic

  3. Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, Pennsylvania, 19111, USA

    Richard R. Hardy

  4. GenPharm International Inc., 297 North Bernardo Avenue, Mountain View, California, 94043, USA

    Dennis Huszar

  5. Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, 48109, USA

    Sally A. Camper

Authors
  1. Ching Chen
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  5. Dennis Huszar
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  6. Sally A. Camper
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  7. Martin Weigert
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Chen, C., Nagy, Z., Radic, M. et al. The site and stage of anti-DNA B-cell deletion. Nature 373, 252–255 (1995). https://doi.org/10.1038/373252a0

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