Immunoglobulins and complement in demyelination induced in mice by Theiler's virus

Area of Science:

• Neuroimmunology
• Virology
• Demyelinating Diseases

Background:

• Theiler's murine encephalomyelitis virus (TMEV) causes chronic demyelination and persistent central nervous system (CNS) infection in SJL mice.
• Elevated immunoglobulin G (IgG) and oligoclonal bands in cerebrospinal fluid (CSF) are observed in TMEV-infected mice, similar to multiple sclerosis.

Purpose of the Study:

• To investigate the roles of humoral immunity and complement in TMEV-induced myelin destruction.
• To determine if the immune response targets myelin components or viral antigens.

Main Methods:

• Intracerebral TMEV inoculation in SJL mice.
• Analysis of IgG and complement (C3) in serum and CSF.
• Immunoblotting and immunoelectron microscopy to detect antigen binding.
• Complement depletion using cobra venom factor.

Main Results:

• IgG in TMEV-infected mice primarily targeted viral antigens, not myelin components.
• Complement component C3 was found in CNS blood vessel walls, not on myelin.
• Complement depletion led to significantly more demyelinating lesions.
• IgG was rarely found on myelin sheaths.

Conclusions:

• Humoral immunity directed at TMEV antigens does not appear to be the primary cause of CNS demyelination in this model.
• The humoral immune response may influence TMEV spread or persistence within the CNS.