The origin of anti-nuclear antibodies in bcl-2 transgenic mice

Laura Mandik-Nayak, Sudhir Nayak, Caroline Sokol, Ashlyn Eaton-Bassiri, Michael P. Madaio, Andrew J. Caton, Jan Erikson

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have shown that anti-dsDNA a cells are actively tolerized in BALB/c mice as manifested by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice increased the lifespan of anti-dsDNA a cells, but did not alter the other features of tolerance, indicating that the anergy of the anti-dsDNA a cells is independent of their reduced lifespan. Furthermore, these data suggest that the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of a cell anergy; rather they may originate from a cells that have transited through a germinal center.

Original languageEnglish (US)
Pages (from-to)353-364
Number of pages12
JournalInternational Immunology
Volume12
Issue number3
DOIs
StatePublished - 2000

Keywords

  • Anti-nuclear antibodies
  • Apoptosis
  • Autoimmunity
  • Germinal center
  • Tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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