Temperature sensitivity of bat antibodies links metabolic state with antigen-recognition diversity

Abstract

Bat immune system features multiple unique properties such as dampened inflammatory responses and increased tissue protection, explaining their long lifespan and tolerance to viral infections. Here, we demonstrated that body temperature fluctuations corresponding to different physiological states in bats exert a dramatic impact on their antibody repertoires. At elevated temperatures typical for flight, IgG from Myotis myotis and Nyctalus noctula showed elevated antigen binding strength and diversity, recognizing both pathogen-derived antigens and autoantigens. The opposite was observed at temperatures reflecting inactive physiological states. This behavior was not observed for IgG antibodies of human and other mammals, or antibodies of birds. Importantly, diversification of bat antibody specificities resulted in preferential recognition of damaged endothelial and epithelial cells, indicating an anti-inflammatory function. The temperature-sensitivity of bat antibodies was mediated by the variable regions of immunoglobulin molecules. Additionally, we revealed specific molecular features of bat IgG such as low thermodynamic stability and implication of hydrophobic interactions in antigen binding as well as high prevalence of polyreactivity. Overall, our results extend the understanding of bat tolerance to disease and inflammation and highlight the link between metabolism and immunity. This might have important repercussions for human health in the future.