ABSTRACT
Several drugs or toxic agents are known to induce autoimmune manifestations in human or experimental situations. The mechanism of these drug-induced disorders is however badly understood. During the last few years we have developed an experimental model in the rat using HgCl2 as an inducing agent. Among the strains tested, the Brown-Norway (BN) strain appeared to be the most susceptible. This strain bears the RTln haplotype at the major histocompatibility complex. Lewis rats (RT11) are resistant. We showed that HgCl2-injected BN rats develop an autoimmune glomerulonephritis. 1 The autoimmune glomerulonephritis observed in this model is biphasic. During the 2nd and 3rd week, anti-glomerular basement membrane (GBM) antibodies are produced which are responsible for the linear pattern of fixation observed by immunofluorescence. From the end of the 1st month a granular pattern of fixation of the fluoresceinated anti-rat IgG antiserum is observed. The origin of these deposits is still unknown. They could be due to the deposition of circulating immune complexes, or alternatively, to the binding of free-circulating antibodies to an irregularly distributed antigen in the glomerular capillary wall as recently described in Heymann’s nephritis. Several antibodies to self (DNA) and non-self antigens (TNP, sheep red blood cells) are also produced. This suggested that HgCl2 triggered polyclonally BN rat B cells. This hypothesis was still strengthened since we observed that mercury-injected BN rats exhibited a hyperimmunoglobulinemia mainly affecting the total serum IgE level. Other experiments have shown that HgCl2-induced polyclonal activation of B cells required the presence of T cells both in vitro and in vivo and that autoreactive T cells were probably at play. It is also important to note that this autoimmune disease is spontaneously autoregulated. Autoimmune abnormalities appear from day 8, reach a plateau during the 2nd and 3rd week, and then decline although HgCl2 injections are pursued. 1
