Formation of the intestinal microbiota during mouse weaning promotes maturation of the IgA repertoire after growth

Abstract

Secretory IgA (sIgA) is a class of antibodies that plays a pivotal role in mucosal immunity. The sIgA secreted into the intestinal tract acts to prevent luminal pathogens and food antigens from penetrating across the intestinal epithelial barrier, thereby contributing to the suppression of infections and food allergies. Furthermore, it binds extensively to symbiotic bacteria, exerting a significant impact on the gut microbiota. The antigen recognition specificity of antibodies is determined by the amino acid sequence of the variable region. Therefore, the type of IgA repertoire influences the formation and maintenance of the gut microbiota and susceptibility to infection and food allergy. The initial repertoire of IgA is induced by the extensive colonization of intestinal bacteria during the weaning period and is maintained for an extended period. However, the relationship between the initial gut microbiota and IgA repertoire development has yet to be fully analyzed. In the present study, the weaning gut microbiota was disrupted with antibiotics, and the IgA repertoire was subsequently analyzed in young adulthood. The administration of antibiotics during the weaning period resulted in the suppression of somatic hypermutation in the variable regions of IgA expressed in the small intestine, as well as an impact on multivalent reactivity in IgA during early childhood. Additionally, disturbances in the weaning gut microbiota led to alterations in the microbiota structure of adolescent mice. These findings suggest that the weaning gut microbiota plays a role in promoting the maturation of IgA function.