Persistence of functionally compromised anti-double-stranded DNA B cells in the periphery of non-autoimmune mice.
Both anti-single-stranded (ss) and anti-double-stranded (ds) DNA antibodies are associated with the autoimmune disease systemic lupus erythematosus (SLE), but only anti-dsDNA antibodies are considered one of the diagnostic criteria. Using Ig transgenes coding for anti-DNA we have determined the fate of anti-dsDNA B cells in a non-autoimmune environment. In a Rag-2 wild-type background, B cells expressing the anti-dsDNA Ig transgenes are present in the spleen but dsDNA specificity is disrupted due to expression of endogenous L chains. In a Rag-2-deficient background where co-expression of endogenous Ig is blocked, splenic B cells expressing only the anti-dsDNA transgene Ig are present, indicating that endogenous Ig expression is not required for bone marrow export. The anti-dsDNA B cells that persist are profoundly crippled in that they are unable to proliferate to lipopolysaccharide or anti-Ig stimulation. Furthermore, these anti-dsDNA Ig transgene B cells show a decreased lifespan relative to non-transgene BALB/c B cells. Persistence of anti-dsDNA B cells in the periphery of non-autoimmune mice raises the possibility that their appearance in the context of SLE is due to their reactivation by T cell help.
Roark
J H
JH
Wistar Institute, Philadelphia, PA 19104, USA.
Bui
A
A
Nguyen
K A
KA
Mandik
L
L
Erikson
J
J
D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D004247:DNA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007145:Immunoglobulin kappa-Chains / Q000276:immunology / Q000378:metabolism; D007136:Immunoglobulins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014162:Transfection
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007136:Immunoglobulins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D004247:DNA