MERCURY-INDUCED RENAL IMMUNE-COMPLEX DEPOSITS IN YOUNG (NZB X NZW)F-1MICE - CHARACTERIZATION OF ANTIBODIES AUTOANTIBODIES/

It is well demonstrated that mercury induces a systemic autoimmune dis ease in susceptible mouse strains. One of the major characteristics of mercury-induced autoimmune-disease in mice is the development of rena l immune complex deposits. We have previously shown that continual inj ection of mercury into young autoimmune prone (NZB x NZW)F-1 mice indu ced an increase in antibody/ autoantibody production as well as develo pment of early renal immune complex deposits. Tn the present study, we characterized the isotype, the specificity and the possible pathogeni city of deposited immunoglobulins in the kidneys of mercury-injected ( NZB x NZW)F-1 hybrids. We found that young (NZB x NZW)F-1 mice injecte d with mercuric chloride (HgCl2) for 6 weeks developed intense antibod y formation of all immunoglobulin isotypes (except for IgG2b) as well as high levels of granular deposits of IgM, IgG1, IgG2a and IgG3 antib odies in the renal mesangium. Increased levels of the same antibody is otypes were also found in the kidney eluate of mercury-but not saline- injected mice. The dominant antibody in the kidney eluate of mercury-i njected mice was of IgG1 isotype and found to be directed against doub le-stranded DNA, collagen, cardiolipin, phosphatidylethanolamine, and the hapten trinitrophenol, but not against nucleolar antigens. Further studies demonstrated that mercury-induced renal immune complex deposi ts in young (NZB x NZW)F-1 mice did not lead to a severe kidney injury . Thus, in response to mercury, young (NZB x NZW)F-1 mice develop rena l immunoglobulin deposits with an isotype and specificity pattern corr elating with that seen in the spleen and in the serum.