Innate virus-sensing pathways in B cell systemic autoimmunity

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Vertebrates possess both innate and adaptive immunity.
• Adaptive immunity relies on somatically generated antigen receptors, which can lead to autoimmunity.
• Innate immunity is crucial for initiating adaptive antiviral responses.

Purpose of the Study:

• To review how inborn errors of innate immunity can cause B cell autoimmunity.
• To explore the mechanisms linking innate immune defects to autoimmune diseases.

Main Methods:

• Review of existing literature on innate immunity and autoimmunity.
• Analysis of signaling pathways involved in B cell tolerance and activation.
• Categorization of autoimmune syndromes based on underlying innate immune defects.

Main Results:

• Defects in innate immunity, particularly increased nucleic acid sensing, can break B cell tolerance.
• These defects activate TLR7, cGAS-STING, or MAVS signaling pathways.
• Syndromes range from chilblain and systemic lupus erythematosus to severe interferonopathies.

Conclusions:

• Inborn errors of innate immunity are a significant cause of B cell autoimmunity.
• Dysregulated nucleic acid sensing is a key mechanism driving these autoimmune conditions.
• Understanding these pathways is crucial for diagnosing and treating autoimmune diseases.