852 Characterizing the microbiota-reactive immune response in neonates lacking breast milk antibodies

Abstract

The human gut microbiome has approximately 1000 bacterial species. To maintain intestinal health, neonates must mount a specialized immune response to allow growth of commensal microbes while limiting pathogenic tissue access. The neonatal immune system is relatively immature, thus immune cells in breast milk are important contributors to establishing appropriate host-microbiome interactions in early life. Previous work in mice shows that neonates lacking breast milk antibodies (matAbs) have increased immune response in gut lymphoid tissue, including greater presence of T-cell dependent germinal center (GC) B cells. Little is known about the function nor the persistence of these GC B cells in neonates. Here we seek to characterize the antibody isotype produced by GC B cells in matAb deficient pups and determine the relative longevity of this antibody response. This study paves the way for understanding the implications of breastfeeding on the neonate gut microbiome. An experimental group of mice were breastfed milk lacking antibodies. These mice were further divided into two groups, one of which was treated with a blocking antibody (anti-ICOSL) to prevent formation of GC B cells. Half of a control population breastfed by WT dams was treated with anti-ICOSL antibody. Feces collected from these four experimental groups from weeks 3-9 were used in ELISAs to quantify IgA abundance. Our data indicates no significant difference in amounts of IgA in mice receiving matAbs compared to those that were not. There is no difference in IgA concentrations in mice whose GC B cell formation was limited by anti-ICOSL treatment compared to control groups. A trend supporting a relative increase in IgA over weeks 3-9 of life was present. Although neonates that do not receive matAbs in breastmilk have increased GC B cells, these cells do not produce more IgA compared to WT. Further research is indicated to determine if the increased GC B cell population in matAb deprived neonates causes an increase in other antibody isotypes or has other aberrant affects on the developing microbiome.