Induction of autoantibodies in normal mice by injection of nucleobindin and natural occurrence of antibodies against nucleobindin in autoimmune MRL/lpr/lpr mice.
Our previous works have shown that nucleobindin (Nuc) or recombinant (r) Nuc not only augments anti-DNA antibody production in vitro but also accelerates autoimmune response in vivo in MRL/+/+ (MRL/n) mice which are the substrain of autoimmune MRL/lpr/lpr (MRL/l) mice. To investigate whether rNuc can induce autoimmune response similarly in naive mice, we carried out intraperitoneal (i.p.) injection of rNuc (5 micrograms) without adjuvant into 8-week-old female BALB/c mice and continued injection twice a week for 12 weeks. About 5 weeks after the first injection, all the mice began to show IgG hypergammaglobulinemia (HG) followed by elevation of a number of autoantibodies of the IgG class such as anti-double-stranded (ds) DNA, anti-U1 ribonuclear protein (RNP), anti-ssB(La) and anti-Fc antibodies (RF), but not by anti-Sm antibodies. However, the IgG anti-dsDNA antibody response and histopathological changes in the kidney of these BALB/c mice were not so noticeable as those in MRL/n mice induced by rNuc in our previous experiment. In contrast, the IgG anti-rNuc antibody response of normal BALB/c mice induced by rNuc was stronger than that of MRL/n mice induced by rNuc. Since the titers of each autoantibody of BALB/c mice induced by rNuc were not always associated with the level of IgG HG, and either IgG HG or IgG autoantibodies could not be induced by control administration of extracts (5 micrograms) of Escherichia coli with or without harboring plasmid alone, polyclonal B cell activation (PBA) appeared not to be the mechanism of this autoimmunity.(ABSTRACT TRUNCATED AT 250 WORDS)
Kanai
Y
Y
Department of Molecular Oncology, University of Tokyo, Japan.
Takeda
O
O
Miura
K
K
Amagai
M
M
Kaneko
T
T
Kubota
T
T
Kanai
Y
Y
Tanuma
S
S
Kurosawa
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000097:blood; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D002135:Calcium-Binding Proteins; D004247:DNA / Q000097:blood / Q000276:immunology; D004268:DNA-Binding Proteins / Q000276:immunology*; D005260:Female; D006133:Growth Substances / Q000276:immunology*; D007113:Immunity, Innate; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D011994:Recombinant Proteins / Q000276:immunology; D017412:Ribonucleoprotein, U1 Small Nuclear / 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; D017412:Ribonucleoprotein, U1 Small Nuclear; C035356:SS-A antibodies; C035357:SS-B antibodies; D004247:DNA