BCL-2 TRANSGENIC LPR MICE SHOW PROFOUND ENHANCEMENT OF LYMPHADENOPATHY

The lpr gene encodes a defective form of the fas gene that mediates ap optosis, and its expression results in autoantibodies and massive lymp hadenopathy. bcl-2, another gene locus that affects programmed cell de ath, acts to inhibit apoptosis. Since multiple mechanisms controlling programmed cell death may contribute to systemic autoimmunity, the eff ect of the bcl-2 transgene on the lpr model was examined by crossing b cl-2 transgenic and C57BL/6-lpr mice. Compared with bcl-2(-)/lpr mice, bcl-2(+)/lpr showed dramatic increases in lymphadenopathy and T cell accumulation, but not in autoantibodies or B cell numbers. Short term transfer studies demonstrated that double negative T cells normally ha ve a limited lifespan, and their survival is enhanced by the bcl-2 tra nsgene. Thus, defects in separate apoptosis mechanisms may combine to produce enhanced pathologic effects.