MERCURY INDUCES POLYCLONAL B-CELL ACTIVATION, AUTOANTIBODY PRODUCTIONAND RENAL IMMUNE-COMPLEX DEPOSITS IN YOUNG (NZBXNZW)F1 HYBRIDS

It is well established that in susceptible mouse strains, chronic trea tment with subtoxic doses of mercuric chloride (HgCl2) induces a syste mic autoimmune disease, which is characterized by increased serum leve ls of IgG1 and IgE antibodies, by the production of anti-nucleolar ant ibodies and by the development of immune complex-mediated glomerulonep hritis. Susceptibility to mercury is partly under the control of major histocompatibility complex genes. To study the susceptibility to merc ury further, we investigated the in vivo effects of mercury in young a utoimmune disease prone (NZB x NZW)F1 (H-2(d/z)) mice prior to establi shment of spontaneous autoimmune disease. Mercury-susceptible SJL (H-2 (s)) mice and mercury low-responder BALB/c (H-2(d)) mice were used as positive and negative controls, respectively. In (NZB x NZW)F1 mice, t reatment with mercury stimulated an intense antibody formation charact erized by increased numbers of splenic IgG1 and IgG3 antibody-producin g cells as well as by elevated serum IgE levels. Injection with mercur y also induced an increased production of IgG1, IgG2b and IgE antibodi es in SJL, but not in BALB/c mice. The mercury-induced IgG1 response i n (NZB x NZW)F1 and SJL mice was found to be polyclonal and autoantibo dies against double-stranded (ds)DNA, IgG, collagen, cardiolipin, phos phatidylethanolamine as well as antibodies against the hapten trinitro phenol were produced. In addition, SJL, but not (NZB x NZW)F1 or BALB/ c mice, produced IgG1 anti-nucleolar antibodies after treatment with m ercury. Further studies demonstrated that (NZB x NZW)F1 and SJL mice d eveloped high titers of renal mesangial immune complex deposits contai ning IgG1 antibodies 3 weeks after injection with mercury. Thus, a mou se strain genetically prone to develop spontaneous autoimmune diseases is highly susceptible to mercury-induced immunopathological alteratio ns.