Effects of Milk Secretory Immunoglobulin A on the Commensal Microbiota

Secretory immunoglobulin A (SIgA) is intimately involved in the transfer of maternal immunity to the newborn breastfed infant. Recent research demonstrates the significance of SIgA in the initial development of the newborn's microbiota and in the establishment of a tolerogenic immunologic disposition towards nonpathogenic organisms and environmental antigens. SIgA has long been known to prevent pathogen binding to the host epithelium through immune exclusion involving numerous mechanisms. This process primarily involves T-cell-dependent, somatically hypermutated monoclonal antibodies with high specificity towards pathogen surface antigens, and the success of the immune response is dependent upon the specific antigen recognition. Whereas this role is important, there is an alternate, dual role for SIgA in the health of the host - protection and promotion of commensal colonization and maintenance of homeostatic immunity. This latter role is primarily dependent upon N- and O-glycan moieties lining the secretory component and heavy chain of the SIgA dimer, with interactions independent of immunoglobulin specificity. These SIgA molecules are nonspecific polyclonal antibodies generated from plasma cells activated by dendritic cell sampling of luminal contents in the absence of inflammation. Breast milk is the primary supply of such polyclonal polyreactive SIgA in the initial stages of neonatal colonization, and it provides vital pathogen resistance while promoting colonization of commensal microbiota.