These authors contributed equally to the study.
Agonistic antibodies to Fas induce a breach in the endothelial lining of the liver and a breakdown in B cell tolerance
Article first published online: 21 DEC 2006
Clinical & Experimental Immunology
Volume 147, Issue 2, pages 346–351, February 2007
How to Cite
Newkirk, M. M., Nowak, U., Skamene, E., Iera, D. and Desbarats, J. (2007), Agonistic antibodies to Fas induce a breach in the endothelial lining of the liver and a breakdown in B cell tolerance. Clinical & Experimental Immunology, 147: 346–351. doi: 10.1111/j.1365-2249.2006.03279.x
- Issue published online: 5 JAN 2007
- Article first published online: 21 DEC 2006
- Accepted for publication 9 November 2006
- liver damage;
- rheumatoid factor
Liver disease can be associated with a breakdown in self-tolerance and the production of autoantibodies such as rheumatoid factors (RF), which bind to IgG. Here we investigated whether primary, non-infectious liver damage was sufficient to induce autoantibody production. We established a model of targeted liver damage induced by weekly sublethal injections of pro-apoptotic anti-Fas (CD95) antibodies. Liver damage, monitored by measurements of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, was minimal 1 week after anti-Fas injection. However, the sublethal Fas stimulation was sufficient to trigger significant haemorrhage in the liver, as assessed by Evans Blue dye leakage into the organ 5 h after anti-Fas antibody injection. We observed an induction of RF in response to the weekly injections of sublethal anti-Fas antibodies but not of isotype control antibodies, indicating a breakdown of self-tolerance induced by Fas engagement. RF induction was unlikely to be due to direct activation of B cells, as splenocytes stimulated with anti-Fas antibodies in vitro did not produce RF. These studies show that sublethal damage to the liver by Fas engagement leads to liver haemorrhage and is sufficient to trigger the breakdown of self-tolerance.