Aberrant IgG isotype generation in mice with abnormal behaviors

Area of Science:

• Immunology
• Neuroscience
• Animal Models

Background:

• BTBR mice exhibit behavioral and immunological traits relevant to autism spectrum disorder (ASD).
• Previous studies indicate elevated serum IgG, brain IgG deposits, and anti-brain IgG in BTBR mice compared to control strains.
• Aberrant immune responses are implicated in the pathogenesis of autism.

Purpose of the Study:

• To investigate IgG isotype distribution and brain-reactive IgG in BTBR mice.
• To compare IgG production patterns between BTBR mice and control strains (FVB/NJ mice).
• To explore the role of altered IgG production and deposition in the BTBR mouse model of autism.

Main Methods:

• Comparative analysis of serum and brain IgG levels in BTBR and FVB/NJ mice.
• Quantification of IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) in serum and bone marrow cell cultures.
• Assessment of brain-reactive IgG and IgG deposition in specific brain regions (striatum, substantia nigra, cerebellum, cortex, hippocampus).

Main Results:

• BTBR mice showed significantly higher levels of serum IgG1, IgG2b, and IgG3 compared to FVB/NJ mice.
• Elevated IgG1:IgG2a ratios were observed in BTBR mice, both in serum and bone marrow cell cultures.
• Increased levels of brain-reactive IgG and IgG1 deposition were found in the brains of BTBR mice, particularly in the striatum and substantia nigra.

Conclusions:

• Alterations in IgG isotype production and deposition in the brain are characteristic of the BTBR mouse model.
• These immunological changes in BTBR mice support their utility as a model for studying immune system involvement in autism.
• The findings suggest that aberrant immune reactivities, specifically involving IgG, may contribute to autism pathogenesis.