HLA CLASS II-MEDIATED DEATH IS INDUCED VIA FAS FAS LIGAND INTERACTIONS IN HUMAN SPLENIC B-LYMPHOCYTES/

HLA class II molecules, expressed on the surface of antigen-presenting cells, are responsible for the presentation of antigen-derived peptid es to CD4(-) helper T lymphocytes. Signaling via these molecules initi ates the generation of second messengers leading to programed cell dea th (PCD) of activated B lymphocytes. The present study examined the me chanism of HLA class II-mediated apoptosis and describes the essential role of the molecule Fas and its ligand (Fast). Fast was expressed in B lymphocytes after stimulation via HLA class II or with phorbol este rs. Expression of East. protein was significantly increased in 50% of B lymphocytes after stimulation via HLA class II, and the level of Fas t mRNA was also increased either by activation with phorbol esters and ionomycin or by signaling via HLA class II. Although HLA class II sig naling did not change the expression of the Pas molecule, it did lead to increased sensitivity to Fas-mediated apoptosis. The crucial role o f Fas/FasL interactions was confirmed by the absence of cell death via HLA class II in B cells lacking Fas expression, and by the significan t inhibition of HLA class Ii-mediated apoptosis in the presence of eit her an antagonistic anti-Pas or anti FasL antibody, These data demonst rate Fast expression on activated human B lymphocytes and support the idea that antigen presentation could contribute to the regulation of l ymphocyte populations via Fas and Fast interactions. (C) 1997 by The A merican Society of Hematology.