| Abstract | 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. |
| Authors | E A Reap, N J Felix, P A Wolthusen, B L Kotzin, P L Cohen, R A Eisenberg
(Affiliation: Department of Medicine, University of North Carolina, Chapel Hill 07599, USA.)
|
| Journal | Journal of immunology (Baltimore, Md. : 1950)
(J Immunol)
Vol. 155
Issue 11
Pg. 5455-62
(Dec 1 1995)
ISSN: 0022-1767 UNITED STATES |
| PMID | 7594564
(Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
|
| Chemical References |
- Antigens, CD95
- DNA, Single-Stranded
- Immunoglobulin G
- Immunoglobulin M
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-bcl-2
|
| Topics |
- Animals
- Antigens, CD95
(genetics, immunology)
- Apoptosis
(genetics)
- DNA, Single-Stranded
(immunology)
- Immunoglobulin G
(analysis)
- Immunoglobulin M
(analysis)
- Lymphatic Diseases
(chemically induced, genetics, immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Mutant Strains
- Mice, Transgenic
- Proto-Oncogene Proteins
(genetics)
- Proto-Oncogene Proteins c-bcl-2
- T-Lymphocytes
(immunology)
|
