title: Participation of the Bcl-2 and Fas molecules in experimental apoptosis of spleen B lymphocytes.
abstract: BACKGROUND
  Homeostasis in the immune system is based on equilibrium between rates of cell renewal and cell death. Failure of elimination of undesirable autoreactive B cell clones may lead to autoimmune disorders.
  
  
  OBJECTIVE
  To assess the participation of the Bcl-2 and Fas molecules in the regulation of B lymphocyte death.
  
  
  METHODS
  We used two strains of mice known to have deficient mechanisms of apoptosis, namely the transgenic C57BL/6-E mu-bcl-2-22 expressing the bcl-2 transgene on B cells, and the C57BL/6-lpr/lpr mutant, lacking the expression of a functional Fas molecule. Both strains develop a systemic lupus erythematosus-like disease with serum autoantibodies and splenomegaly. We induced apoptosis by three different treatments: dexamethasone,gamma irradiation and hyperthermia. The proportion of cells in apoptosis was determined with the TUNEL method.
  
  
  RESULTS
  Radiation or hyperthermia induced apoptosis was inhibited more effectively by having the lpr mutation than the proto-oncogene bcl-2, but the latter conferred higher resistance to apoptosis by dexamethasone.
  
  
  CONCLUSIONS
  Our findings suggest that the role of molecules regulating cell death may relate to the stimuli used to induced apoptosis, and that both the lpr mutation and the overexpression of the proto-oncogene bcl-2 protect B cells from apoptosis induced by the three treatments tested.
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Alvarado
authors.forename: M E
authors.initials: ME
authors.lastname: Alarcón-Riquelme
authors.forename: J
authors.initials: J
authors.lastname: Alcocer-Varela
authors.forename: C
authors.initials: C
authors.lastname: Fernández
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D001327:Autoimmune Diseases / Q000235:genetics / Q000473:pathology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005720:Gamma Rays; D006358:Hot Temperature; D007075:Immunoglobulin M / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000502:physiology*; D011519:Proto-Oncogenes; D011993:Recombinant Fusion Proteins / Q000502:physiology; D013154:Spleen / Q000473:pathology*; D019076:Transgenes; D019014:fas Receptor / Q000502:physiology*
chemical_list: D007075:Immunoglobulin M; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D019014:fas Receptor; D003907:Dexamethasone