Antibodies in breast milk: Pro-bodies designed for healthy newborn development

Abstract

This manuscript sheds light on the impact of maternal breast milk antibodies on infant health. Milk antibodies prepare and protect the newborn against environmental exposure, guide and regulate the offspring's immune system, and promote transgenerational adaptation of the immune system to its environment. While the transfer of IgG across the placenta ceases at birth, milk antibodies are continuously replenished by the maternal immune system. They reflect the mother's real-time adaptation to the environment to which the infant is exposed. They cover the infant's upper respiratory and digestive mucosa and are perfectly positioned to control responses to environmental antigens and might also reach their circulation. Maternal antibodies in breast milk play a key role in the immune defense of the developing child, with a major impact on infectious disease susceptibility in both HIC and LMIC. They also influence the development of another major health burden in children-allergies. Finally, emerging evidence shows that milk antibodies also actively shape immune development. Much of this is likely to be mediated by their effect on the seeding, composition and function of the microbiota, but not only. Further understanding of the bridge that maternal antibodies provide between the child and its environment should enable the best interventions to promote healthy development.

Keywords: allergy; breast milk; immune imprinting; immunoglobulins; infection; microbiota; mucosal immunology; neonate.

FIGURE 1

Personalized protection afforded by breast milk antibodies. Breast milk contains immunoglobulins (Ig) trafficked through the mammary gland (MG) epithelium by Fc receptors: PIGR transports IgA and IgM polymers, while FcRn binds IgG and IgE. These Ig have a dual origin: (1) upon lactation, the MG epithelial cells recruit CCR10+ plasma cells, primarily from mucosal sites, by secreting CCL28. These antibody‐secreting cells, in vast majority IgA+, constitute a resident population in the MG throughout lactation and the primary source of milk Ig. (2) Circulating serum Ig (mostly IgG), produced by bone marrow plasma cells, generated by past and current systemic responses, can be transferred to the milk through their binding to FcRn. The milk Ig repertoire reflects the mother's (and by extension, her infant's) environment, and is thus tailored to shape their microbiome and protect them from infection, allergy and gut inflammation. Image created with BioRender.

FIGURE 2

Transgenerational immune imprinting. Maternal antibodies in breastmilk prepare and protect the newborn against environmental exposure, guide and regulate the offspring's immune system, and promote transgenerational adaptation of the immune system to its environment via (1) SIgA in combination with other immunoglobulins directly bind to pathogen antigens neutralizing their toxin and/or ability to damage and invade epithelial cells, and exclude dietary and environmental allergens thus protecting against the development of allergy, (2) promote the shaping of a healthy microbiota, via positively selecting for symbiotic commensals, promoting niche colonization via forming biofilms for symbiotic commensals, and influencing microbial gene expression towards an anti‐inflammatory profile by preventing the production of microbial metabolites or surface proteins that could be harmful to the host, (3) influence immune development by shaping the microbiota (SIgA and IgG), inhibiting T helper effector responses and regulating the immunoregulatory tone of the gut environment (SIgA), controlling B cell activation (IgG), the generation of antigen specific Tregs (IgG‐antigen immune complexe), and the development of ILC3 (IgA‐ maternal microbiota metabolite immune complexe). Image created with BioRender.