Apoptosis abnormalities of splenic lymphocytes in autoimmune lpr and gld mice.
The murine gene lpr encodes an aberrant form of the apoptosis-inducing receptor Fas. The gene gld, which causes an autoimmune syndrome phenotypically identical to that caused by lpr, encodes a mutant Fas ligand. Because the lpr gene must be expressed in both T and B cells to produce autoimmune disease, it might be anticipated that apoptosis abnormalities would be present in both. Therefore, we quantitated apoptosis in T and B cells from lpr, gld, and normal mice in a short-term in vitro culture system. Freshly isolated spleen cells from normal, lpr, or gld mice showed little or no apoptosis as assessed by quantitative DNA flow cytometry. However, after overnight culture, both T and B cells showed substantial spontaneous apoptosis. Such apoptosis increased strikingly with age in normal but not in autoimmune B cells. CD23low B cells, which are prominent in lpr and gld mice, were particularly notable for high levels of programmed cell death in normal mice. The apoptosis caused by the gld defect could not be corrected by coculture with normal spleen cells. The persistence with age of low levels of B cell apoptosis in lpr and gld mice presumably reflects deficient Fas/Fas ligand interactions. The further localization of the B cell apoptosis defect to the unusual CD23low B cells, which accumulate in lpr and gld mice, adds to the evidence that these cells may be of critical importance to autoimmunity.
Reap
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Department of Medicine, University of North Carolina, Chapel Hill 27599.
Leslie
D
D
Abrahams
M
M
Eisenberg
R A
RA
Cohen
P L
PL
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D017209:Apoptosis / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D007075:Immunoglobulin M / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics; D017455:Receptors, IgE / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor
D000954:Antigens, Surface; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D017455:Receptors, IgE; D019014:fas Receptor