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

Ching Chen, Zoltan Nagy, Martin Weigert, Marko Z. Radic, Richard R. Hardys, Dennis Huszari, Sally A. Camper

Research output: Contribution to journalLetter

256 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)252-255
Number of pages4
JournalNature
Volume373
Issue number6511
DOIs
StatePublished - Jan 19 1995

ASJC Scopus subject areas

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    Chen, C., Nagy, Z., Weigert, M., Radic, M. Z., Hardys, R. R., Huszari, D., & Camper, S. A. (1995). The site and stage of anti-DNA B-cell deletion. Nature, 373(6511), 252-255. https://doi.org/10.1038/373252a0