Breast milk IgG engages the mouse neonatal immune system to instruct responses to gut antigens

Maternal antibodies fundamentally regulate gut immunity in the developing infant, yet the mechanisms underlying this process remain elusive. We found that maternal immunoglobulin G (IgG), ingested in the first week of life, restrained microbiota-dependent adaptive immune responses weeks later, after weaning. This activity was linked to maternal antibodies that could bind bacteria in the neonatal gut and the ability of microbe-IgG complexes to engage Fc and complement-dependent effector functions in offspring. Ingestion of microbiota-specific maternal IgG also limited aberrant neonatal responses to dietary antigens encountered at weaning. These discoveries suggest that maternal IgG engages the immune system of offspring in early postnatal life to tune mucosal responses and reinforce intestinal homeostasis in the face of dynamic shifts in food and bacterial antigens during development.