ENHANCED EXPRESSION OF NUCLEOBINDIN IN LYMPHATIC ORGANS OF LUPUS-PRONE MICE

Nucleobindin (Nuc) was originally identified as a 55 kDa protein that enhanced anti-DNA antibody production in cultures of autoimmune MRL/lp r mouse spleen cells. cDNA cloning and the production of recombinant p rotein (rNuc) have revealed that rNuc binds to DNA and Ca2+ by means o f leucine zipper and EF-hand motif structures. In vitro and in vivo ef fects of rNuc to induce autoantibodies including anti-dsDNA antibody i n normal mice have been demonstrated; however, whether Nuc is involved in the state of autoimmunity occurred in MRL/lpr, C3H/gld and male BX SB mice has not been elucidated. Here we report that the expression of Nuc mRNA is upregulated with age in the lymphatic organs and is posit ively correlated to the serum levels of Nuc in these lupus-prone strai ns of mice. Upon immunization with KLH in Freund's complete adjuvant, normal BALB/c mice also showed an elevated level of Nuc in their serum and elevated Nuc mRNA in their lymphatic organs. In addition, in vitr o stimulation of BALB/c splenocytes with Con A or LPS remarkably enhan ced Nuc mRNA expression. These results suggest that upregulation of Nu c mRNA in lymphatic organs and serum Nuc of lupus-prone mice is relate d to spontaneous activation of immunocompetent cells; the present data are also consistent with our previous hypothesis on the role of Nuc i n the induction or enhancement of autoimmunity in lupus models of mice .