Persistence of functionally compromised anti-double-stranded DNA B cells in the periphery of non-autoimmune mice

• Published in: International immunology 1997-11, Vol.9 (11), p.1615-1626
• Main Authors: Roark, J H, Bui, A, Nguyen, K A, Mandik, L, Erikson, J
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Autoimmunity - immunology; B-Lymphocytes - cytology; B-Lymphocytes - immunology; B-Lymphocytes - physiology; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; DNA - genetics; DNA - immunology; DNA - metabolism; DNA, Single-Stranded - genetics; DNA, Single-Stranded - immunology; DNA, Single-Stranded - metabolism; DNA-Binding Proteins - genetics; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Heavy Chains - immunology; Immunoglobulin Heavy Chains - metabolism; Immunoglobulin kappa-Chains - immunology; Immunoglobulin kappa-Chains - metabolism; Immunoglobulin Light Chains - genetics; Immunoglobulin Light Chains - immunology; Immunoglobulin Light Chains - metabolism; Immunoglobulins - biosynthesis; Immunoglobulins - genetics; Immunoglobulins - immunology; Lupus Erythematosus, Systemic - blood; Lupus Erythematosus, Systemic - immunology; Mice; Mice, Inbred BALB C; Mice, Transgenic; Molecular Sequence Data; Mutation; Phenotype; Sequence Homology, Amino Acid; Spleen - cytology; Spleen - immunology; Transfection
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/9.11.1615

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.