Both perforin (pfp) and Fas ligand (FasL) contribute to control of autoreactive B cells and retard lupus like disease in parent-into-F1 mice. (143.45)

• Published in: The Journal of immunology (1950) 2010-04, Vol.184 (1_Supplement), p.143-143.45
• Main Authors: Puliaiev, Maksym, Puliaev, Roman, Puliaeva, Irina, Soloviova, Kateryna, Via, Charles
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.184.Supp.143.45

The transfer of B6 splenocytes into BDF1 (B6->F1) mice results in donor anti-host cytotoxic T cell elimination of host B cells whereas transferring DBA parental splenocytes (DBA->F1) results in a lupus like disease. Using perforin (pfp) or FasL (gld) defective donor T cells we have shown that both pathways are critical for host B cell elimination at two weeks and pfp->F1 mice develop mild lupus long term. The present study compared pfp->F1 vs gld->F1 mice at both two weeks and 10-12 weeks for both males and females to determine if FasL or pfp was more important in controlling B cell hyperactivity and preventing lupus like disease. At two weeks, male gld->F1 mice exhibited significantly better elimination of B cells vs pfp->F1 mice however both groups were significantly impaired compared to B6->F1 mice. Both pfp->F1 and gld->F1 females were defective and did not differ significantly. Long term, female DBA->F1 mice exhibited severe renal disease compared to all other groups. Disease was mild and comparable in both male and female gld->F1 and pfp->F1 mice as measured by proteinuria (1+ or 2+) and autoantibodies. These results demonstrate that both pfp and FasL play important and relatively equivalent roles in controlling autoreactive B cell expansion and progression to lupus-like disease.