Pan IgG repertoire in AlphaGal KO mice

Most mammals carry a functional N-acetyllactosaminide alpha-1,3-galactosyltransferase 1 (GGTA1) gene, which encodes the enzyme synthetizing Galα1-3Galβ1-4Glc (αGal). In contrast, anthropoid monkeys, including humans, carry loss-of-function mutations in GGTA1 and lack αGal (1, 2). Natural selection and fixation of these mutations allowed for the emergence of αGal-specific immunity, enhancing resistance to pathogens expressing αGal (3-5). Here we demonstrate that loss of Ggta1 function in mice enhances resistance to bacterial sepsis, irrespectively of αGal-specific immunity. This is owed instead to enhanced IgG bactericidal activity, driven by improved IgG binding to the Fc gamma receptor IV (FcRIV). As a trade-off, Ggta1 loss of function causes earlier onset of reproductive senescence, a major fitness cost at play during the early stages of hominidae evolution.