Journal
AUTOIMMUNITY
Volume 46, Issue 2, Pages 121-127Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/08916934.2012.748751
Keywords
systemic lupus erythematosus; somatic mutation; anti-DNA antibodies; germinal center
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Funding
- Deutsche Forschungsgemeinschaft [SFB 423]
- Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the Friedrich-Alexander University [A25]
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The formation of antibodies against double-stranded (ds) DNA is considered to be the serologic hallmark of systemic lupus erythematosus (SLE) and anti-dsDNA antibodies play an important role in the pathogenesis of the disease. Anti-dsDNA antibodies from lupus mice and SLE patients arise by somatic mutation. Importantly, autoantibodies in which somatic mutations have been reverted to germ-line V regions did not show any measurable autoreactivity, suggesting that anti-dsDNA autoantibodies develop from non-autoreactive B-cells by somatic hypermutation, presumably during the germinal center reaction. As the random nature of somatic hypermutation will inevitably create autoreactive B cells, self-tolerance checkpoints at the postmutational stage of B cell differentiation have to exist that normally prevent the induction of pathogenic anti-dsDNA specificities. This review summarizes the proposed mechanisms for the generation of anti-dsDNA in murine lupus and in SLE patients.
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