Methyl mercury-induced autoimmunity in mice

Area of Science:

• Immunology
• Toxicology
• Genetics

Background:

• Mercury compounds are environmental toxins with known immunomodulatory effects.
• Methylmercury (MeHg) and inorganic mercury (HgCl2) exhibit distinct toxicological profiles.
• The role of genetic background, particularly the major histocompatibility complex (MHC), in mercury-induced autoimmunity is not fully elucidated.

Purpose of the Study:

• To investigate the induction of antinucleolar antibodies (ANoA) by methylmercury (MeHg) in different mouse strains.
• To determine the genetic control of susceptibility to MeHg-induced autoimmunity, focusing on the major histocompatibility complex (MHC).
• To compare the immunotoxic effects of MeHg and inorganic mercury (HgCl2).

Main Methods:

• Female mice from various strains (SJL/N, A.SW, B10.S (H-2s), BALB/C, DBA/2 (H-2d), A.TL, B10.TL (H-2t1)) were subcutaneously injected with MeHgCl or NaCl.
• Humoral immune responses, including antinucleolar antibody (ANoA) production, polyclonal B-cell activation, and serum IgE levels, were assessed.
• The presence of systemic immune-complex deposits was examined.

Main Results:

• MeHg induced ANoA targeting fibrillarin specifically in H-2s mice, indicating MHC-linked susceptibility.
• Background genes influenced the ANoA titer strength in H-2s mice (A.SW > SJL > B10.S).
• MeHg induced a weaker B-cell response compared to HgCl2, with minimal Th2 cell activation and IgE production; however, delayed demethylation led to a mercury-induced immune response similar to HgCl2.

Conclusions:

• Susceptibility to MeHg-induced antinucleolar antibodies is genetically controlled by the H-2 complex.
• MeHg and HgCl2 exert quantitatively and qualitatively different effects on the murine immune system.
• Genetically susceptible mice remain vulnerable to mercury challenge, unlike rats.