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 als o accelerates autoimmune response in vivo in MRL/ + / + (MRL/n) mice w hich are the substrain of autoimmune MRL/lpr/lpr (MRL/l) mice. To inve stigate whether rNuc can induce autoimmune response similarly in naive mice, we carried out intraperitoneal (i.p.) injection of rNuc (5 mu g ) without adjuvant into 8-week-old female BALB/c mice and continued in jection twice a week for 12 weeks. About 5 weeks after the first injec tion, all the mice began to show IgG hypergammaglobulinemia (HG) follo wed by elevation of a number of autoantibodies of the IgG class such a s anti-double-stranded (ds) DNA, anti-U1 ribonuclear protein (RNP), an ti-ssB(La) and anti-Fc antibodies (RF), but not by anti-Sm antibodies. However, the IgG anti-dsDNA antibody response and histopathological c hanges in the kidney of these BALB/c mice were not so noticeable as th ose in MRL/n mice induced by rNuc in our previous experiment. In contr ast, 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 t he 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 extra cts (5 mu g) of Escherichia coli with or without harboring plasmid alo ne, polyclonal B cell activation (PBA) appeared not to be the mechanis m of this autoimmunity. With the strong autoantigenicity of rNuc in bo th normal and MRL/n mice as a momentum, we found naturally occurring a utoantibodies 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 developme nt of systemic autoimmunity. Taken together, co-factor(s) other than N uc and/or more amounts of Nuc seemed to be necessary for the developme nt of full-blown systemic autoimmunity in naive mice.