Apoptotic Splenocytes Drive the Autoimmune Response to Poly(ADP-ribose) Polymerase 1 in a Murine Model of Lupus

摘要: Although defects in apoptosis have been linked to both human and murine lupus, the exact mechanisms remain unknown. Moreover, it is not clear whether such are primary or secondary events disease pathogenesis. To address these issues, we used an induced model of parent-into-F 1 chronic graft-versus-host (cGVHD) which a lupus-like phenotype highly similar systemic lupus erythematosus reliably normal F mice. We addressed role nuclear Ags modified by caspases during as potential targets autoantibody response our results identify poly(ADP-ribose) polymerase (PARP-1) frequently targeted autoantigen. Additional proteins cleaved were also immune response. Importantly, female mice exhibited significantly greater numbers apoptotic cells germinal centers higher serum anti-PARP-1 Ab levels compared with male cGVHD Serum could be elevated comparable those injection syngeneic splenocytes early course. These provide mechanism autoantibodies target molecules. Specifically, T cell-driven polyclonal B cell activation characteristic sufficient saturate otherwise clearance mechanisms, permitting material accumulate, serve autoantigens, drive production.