The origin of anti-nuclear antibodies in bcl-2 transgenic mice.
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.
Mandik-Nayak
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L
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Nayak
S
S
Sokol
C
C
Eaton-Bassiri
A
A
Madaio
M P
MP
Caton
A J
AJ
Erikson
J
J
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000473:pathology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D019556:COS Cells; D016922:Cellular Senescence; D002522:Chlorocebus aethiops; D017635:Clonal Anergy; D004247:DNA / Q000276:immunology*; D053222:Fas Ligand Protein; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D019254:Genes, bcl-2; D018858:Germinal Center / Q000276:immunology*; D007108:Immune Tolerance; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D008822:Mice, Transgenic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016037:Single-Blind Method; D019076:Transgenes
D000974:Antibodies, Antinuclear; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D004247:DNA