The origin of anti-nuclear antibodies in bcl-2 transgenic mice

Int Immunol. 2000 Mar;12(3):353-64. doi: 10.1093/intimm/12.3.353.


bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have shown that anti-dsDNA B cells are actively tolerized in BALB/c mice as manifested by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice increased the lifespan of anti-dsDNA B cells, but did not alter the other features of tolerance, indicating that the anergy of the anti-dsDNA B cells is independent of their reduced lifespan. Furthermore, these data suggest that the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of B cell anergy; rather they may originate from B cells that have transited through a germinal center.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / biosynthesis*
  • Antibodies, Antinuclear / immunology
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • B-Lymphocyte Subsets / immunology*
  • COS Cells
  • Cellular Senescence
  • Chlorocebus aethiops
  • Clonal Anergy*
  • DNA / immunology*
  • Fas Ligand Protein
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin*
  • Genes, bcl-2*
  • Germinal Center / immunology*
  • Immune Tolerance
  • Lupus Nephritis / genetics
  • Lupus Nephritis / immunology
  • Lupus Nephritis / pathology
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred MRL lpr
  • Mice, Transgenic
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Recombinant Fusion Proteins / physiology
  • Single-Blind Method
  • Transgenes*


  • Antibodies, Antinuclear
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • DNA