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Murine susceptibility to mercury. II. autoantibody profiles and renal immune deposits in hybrid, backcross, and H-2d congenic mice.

Authors
  • Hultman, P
  • Bell, L J
  • Eneström, S
  • Pollard, K M
Type
Published Article
Journal
Clinical immunology and immunopathology
Publication Date
Jul 01, 1993
Volume
68
Issue
1
Pages
9–20
Identifiers
PMID: 8513597
Source
Medline
License
Unknown

Abstract

Inorganic mercury causes systemic autoimmunity and/or immune-complex deposits in strains of mice carrying certain H-2 haplotypes, for example H-2s and H-2d. This study aimed at describing the genetic mechanisms regulating these reactions. Inbred SJL, C57BL/6J (B6), C57BL/10J (B10), and DBA mice, F1(SJL x DBA), F1(SJL x B6), and F2(SJL x B6) hybrids, and mice derived from a backcross of SJL or B6 mice to F1(SJL x B6) hybrids were given subcutaneous injections of either 1.6 mg HgCl2/kg body wt or 0.1 ml NaCl every third day for 6 weeks. SJL mice developed a high titer of serum antinucleolar antibodies (ANoA) of the IgG class targeting the nucleolar protein fibrillarin and a significantly increased titer of IgG and C3 colocalized as granular deposits in the renal mesangium and vessel walls. The B6 and DBA strains lacked ANoA and showed no increase in titers of immune deposits. Nine percent of mercury-treated F1(SJL x DBA) hybrids developed IgG-ANoA which were of a low titer, and only occasional hybrids showed an increased titer of granular mesangial IgG deposits. Mercury treatment induced ANoA of low titer in 41% of F1(SJL x B6) hybrids, and 24% had increased granular mesangial immune deposits. Four of 61 mercury-treated BC-[SJL x F1(SJL x B6)] mice showed ANoA which were of a high titer and targeted the nucleolar protein fibrillarin. ANoA were not found in 55 mercury-treated F2(SJL x B6) hybrids or in 56 mercury-treated mice derived from a backcross of B6 mice to F1(SJL x B6) hybrids. Increased mesangial immune deposits were regularly accompanied by vessel wall deposits in F1- and F2(SJL x B6) hybrids, but only 53% of BC(SJL x F1[SJL x B6]) mice with increased mesangial deposits had vessel wall deposits. Vessel wall immune deposits were only present in mice with increased mesangial deposits. A majority of mice which developed significantly increased titers of mesangial IC deposits showed no ANoA. In conclusion, the susceptibility in SJL mice to develop ANoA during mercury treatment, which has been shown to reside in the H-2A locus, was codominantly inherited in a cross with mice carrying the H-2b and H2d haplotypes. Non-H-2 genes dampened ANoA expression to a degree which varied between the strains. Since renal vessel and mesangial IC deposits developed in backcross mice lacking serum ANoA, these deposits must contain IC not related to fibrillarin-antifibrillarin.(ABSTRACT TRUNCATED AT 400 WORDS)

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