Overexpression of the antiapoptotic gene Bfl-1 in B cells from patients with familial systemic lupus erythematosus.
Genetic determinants taking part in the development of systemic lupus erythematosus (SLE) are complex and not fully characterized. Dysregulated expression of genes involved in the control of apoptosis has been previously suggested. We report here a consanguineous family with SLE manifestations in three siblings associated in one of them with severe lymphoproliferative features. Laboratory studies showed no defect in CD95-mediated cell death. Screening expression of Bcl-2 family genes that regulate mitochondrial apoptosis pathway showed an overexpression of the antiapoptotic Bfl-1 gene. Real time RT-PCR analysis indicated that overexpression of Bfl-1 was restricted to B-cells, with normal expression in T-cells. Those results suggest that overexpression of Bfl-1 could result in impaired B-lymphocyte homeostasis and inappropriate immune response leading to autoimmune manifestations.
Andre
J- M
J
Service d'immuno-hématologie pédiatrique, Hôpital Debrousse, Hospices Civils de Lyon, Lyon, France.
Cimaz
R
R
Ranchin
B
B
Galambrun
C
C
Bertrand
Y
Y
Bouvier
R
R
Rieux-Laucat
F
F
Trescol-Biemont
M C
MC
Cochat
P
P
Bonnefoy-Berard
N
N
D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D015778:Minor Histocompatibility Antigens; D010375:Pedigree; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*
C096816:BCL2-related protein A1; D015778:Minor Histocompatibility Antigens; D019253:Proto-Oncogene Proteins c-bcl-2