INTRODUCTION
In mammals, the early-life period after birth is a time of profound immune development during which the generation of appropriate responses to newly encountered commensal and environmental antigens is crucial for maintaining health. Breast milk is positioned to regulate nascent mucosal immune responses through the delivery of live microbes, commensal-selecting oligosaccharides, maternal cells, and immunomodulatory factors, such as antibodies, directly to the infant gut. By defining the beneficial components of breast milk and the mechanisms by which they function, we may advance strategies to boost healthy immunity in early life and beyond.
RATIONALE
Numerous studies in mice and humans support a central function for breast milk antibodies in establishing healthy gut immunity, yet the mechanisms underlying this process are not clear. Existing models, largely based on lumenal immunoglobulin A (IgA) in adults, overlook critical physiological features of early life, including an immature gut barrier, dynamic microbiota, and the presence of multiple breast milk–derived antibody isotypes (IgA, IgG, and IgM) in the infant lumen. We developed a strategy to dissect the specific contributions, timing, and function of breast milk antibodies during the postnatal period.
RESULTS
Using an established mouse model of maternal antibody deficiency in which offspring were cross-fostered at various postnatal time points, we found that ingestion of breast milk antibodies in the first week of life served to restrain germinal center T follicular helper cell (TFH cell) and B cell responses weeks later, after weaning. This elevated immune response was specific to gut-associated lymphoid tissues and was attenuated in sterile animals lacking a gut microbiota. Feeding mouse pups during the first 7 days of life with IgG purified from milk or serum was sufficient to restrain later immune dysregulation. Although the ability of ingested IgG to bind neonatal gut bacteria was linked with its protective functions, it did not cause changes in microbiota composition or gut barrier function. Unlike IgA, mouse IgG can directly engage with the immune system through antibody (Fc) receptors and the complement pathway. Neonatal immune cells in the intestinal lamina propria and epithelium expressed multiple Fc and complement receptors, and oral IgG administration was unable to dampen aberrant immunity in offspring deficient in these IgG-sensing systems. Last, we found that feeding pups microbiota-reactive IgG in the first week of life served to limit offspring susceptibility to colitis and prevent aberrant allergic responses to food antigens during the weaning transition.
CONCLUSION
Breast milk antibodies play a vital role in shaping early-life intestinal homeostasis. Our data support a model in which breast milk IgG interacts with gut bacteria and antibody-sensing systems in young mice to dampen subsequent immune responses to gut microbial and dietary antigens encountered during weaning. This broad, protective effect of maternal IgG may represent an evolutionary strategy by which mammals promote tolerogenic responses to the diverse antigens introduced during this developmental period.
2 Medical News 