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 μg) 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 μg) of Escherichia coli with or without harboring plasmid alone, polyclonal B cell activation (PBA) appeared not to be the mechanism of this autoimmunity. With the strong autoantigenicity of rNuc in both normal and MRL n mice as a momentum, we found naturally occurring autoantibodies against rNuc in the sera of autoimmune MRL l mice. Since Nuc is present in the sera of autoimmune MRL l mice ranging from 100 to 600 ng/ml, but under the detectable level in MRL n mice, Nuc and/or the IgG response against Nuc may play a crucial role in the development of systemic autoimmnity. Taken together, co-factor(s) other than Nuc and/or more amounts of Nuc seemed to be necessary for the development of full-blown systemic autoimmunity in naive mice.