Novel autoimmune phenomena induced in vivo by a new DNA binding protein Nuc: a study on MRL/n mice.
We previously purified a 55 kDa protein that preferentially expands anti-DNA antibody production both in vitro and in vivo across the H-2 barrier from culture supernatants of KML1-7 cells, cloned from a lupus-prone MRL/lpr mouse. By using the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced recombinant(r) Nuc in Escherichia coli. To elucidate the function of rNuc in vivo, we initially injected intraperitoneally 5 micrograms of rNuc without adjuvant into female MRL/n mice at 8 weeks of age and continued injection twice a week. As early as 5 weeks after administration, all mice treated showed an increase in IgG anti-double stranded (ds) DNA antibodies accompanied by IgG hypergammaglobulinemia (HG). Of particular interest was that these mice also produced anti-U1RNP antibodies and rheumatoid factor (RF) of IgG class, but not anti-Sm antibodies. Histopathologically, hypercellularity with occasional crescents in the glomeruli was observed, but evidence for lupus nephritis was lacking, indicating that some factors other than Nuc are necessary for the development of a lupus syndrome observed in MRL/lpr mice. Similar administration of lipopolysaccharide into MRL/n mice failed to induce autoantibodies except for a slight increase in serum IgG, suggesting that these autoimmune responses are not due simply to polyclonal B-cell activation. The presence of rNuc will give us a clue for further understanding of autoimmunity.
Kanai
Y
Y
Department of Molecular Oncology, University of Tokyo, Japan.
Takeda
O
O
Kanai
Y
Y
Miura
K
K
Kurosawa
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000032:analysis; D001323:Autoantibodies / Q000276:immunology*; D015551:Autoimmunity; D002135:Calcium-Binding Proteins; D004247:DNA / Q000032:analysis; D004268:DNA-Binding Proteins / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006133:Growth Substances / Q000008:administration & dosage / Q000276:immunology*; D006942:Hypergammaglobulinemia / Q000209:etiology / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012217:Rheumatoid Factor / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D006133:Growth Substances; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D011994:Recombinant Proteins; D012261:Ribonucleoproteins; D004247:DNA; D012217:Rheumatoid Factor