Innate virus-sensing pathways in B cell systemic autoimmunity
Carola G. Vinuesa, Amalie Grenov, George Kassiotis
Abstract
Although all multicellular organisms have germ line-encoded innate receptors to sense pathogen-associated molecular patterns, vertebrates also evolved adaptive immunity based on somatically generated antigen receptors on B and T cells. Because randomly generated antigen receptors may also react with self-antigens, tolerance checkpoints operate to limit but not completely prevent autoimmunity. These two systems are intricately linked, with innate immunity playing an instrumental role in the induction of adaptive antiviral immunity. In this work, we review how inborn errors of innate immunity can instigate B cell autoimmunity. Increased nucleic acid sensing, often resulting from defects in metabolizing pathways or retroelement control, can break B cell tolerance and converge into TLR7-, cGAS-STING-, or MAVS-dominant signaling pathways. The resulting syndromes span a spectrum that ranges from chilblain and systemic lupus to severe interferonopathies.