bcl-2 transgenic Lpr mice show profound enhancement of lymphadenopathy.
The lpr gene encodes a defective form of the fas gene that mediates apoptosis, and its expression results in autoantibodies and massive lymphadenopathy. bcl-2, another gene locus that affects programmed cell death, acts to inhibit apoptosis. Since multiple mechanisms controlling programmed cell death may contribute to systemic autoimmunity, the effect of the bcl-2 transgene on the lpr model was examined by crossing bcl-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 have a limited lifespan, and their survival is enhanced by the bcl-2 transgene. Thus, defects in separate apoptosis mechanisms may combine to produce enhanced pathologic effects.
Reap
E A
EA
Department of Medicine, University of North Carolina, Chapel Hill 07599, USA.
Felix
N J
NJ
Wolthusen
P A
PA
Kotzin
B L
BL
Cohen
P L
PL
Eisenberg
R A
RA
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004277:DNA, Single-Stranded / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008206:Lymphatic Diseases / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D013601:T-Lymphocytes / Q000276:immunology; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology
D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor