Aberrant expression of Fas ligand on anti-DNA autoantibody secreting B lymphocytes in patients with systemic lupus erythematosus: 'immune privilege'-like state of the autoreactive B cells.

摘要

BACKGROUND: Fas/Fas ligand (FasL) system has been assigned a pivotal role in the development and maintenance of peripheral tolerance, and mice with defects in their Fas/FasL system develop lupus-like symptoms. In this study we examined FasL expression of peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE). METHODS: We assessed FasL mRNA and protein expression by reverse transcription (RT)-PCR and immunoblotting and immunocytochemical staining, respectively, in patients with SLE. Anti-DNA antibody secreting B cells were purified using biotin labeled DNA and streptavidin-bead. RESULTS: Expression of FasL protein was not or very weakly detected in freshly isolated PBMC in normal individuals. In contrast, freshly isolated SLE PBMC exhibited the enhanced expression of FasL protein without in vitro stimulation. Not only purified T cells but also purified B cells expressed FasL on their cell surface spontaneously. In addition, freshly isolated anti-DNA autoantibody secreting B cells express FasL without in vitro stimulation. CONCLUSION: The results suggest that autoreactive B lymphocytes which aberrantly express FasL may kill Fas+ immunoregulatory T lymphocytes. Thus aberrantly expressed FasL may facilitate escape of the autoreactive B cells from the immune tolerance system, and may contribute to the sustained secretion of autoantibodies in patients with SLE.