Does early life translocation of commensal microbes shape humoral immunity? Jamal Green, Jean-Bernard Lubin PhD, Sarah Maddux, Tereza Duranova, Lidiya Denu, Matthew Sullivan, & Michael Silverman MD/PhD Children’s Hospital of Philadelphia, University of Pennsylvania In mice and humans, there is growing evidence that early-life microbial interactions impact long-term immune system function. Without microbial colonization during the first weeks of life, a normal immune system does not develop. Even if microbes are introduced during adulthood, immune components such as invariant natural killer T cells and allergic IgE responses do not return to physiological levels. Furthermore, if the microbiota is perturbed with antibiotics during early life, there is increased susceptibility to pathological inflammation, autoimmunity, or cancer later in life. The Silverman lab demonstrated that autoimmunity in the non-obese diabetic (NOD) murine model of diabetes is affected by the early life microbial environment as well (PNAS, 2017). These studies demonstrate that critical immunological interactions with microbiota occur in early life, yet the underlying mechanisms of peripheral immune education remain elusive. Further, the specific location for these key microbiota-immune system interactions have not been clearly defined. We hypothesize that translocation of live commensal bacteria from the intestines to the mesenteric lymph node during the early life period is a critical physiologic mechanism for the education of the immune system. To rigorously study the early-life microbiota, we developed a novel consortium of 9 culturable bacteria (PedsCom) that represent over 90% of the intestinal bacteria in pre-weaning NOD mice. In healthy mice and humans, systemic IgGs capable of binding a subset of commensals develop shortly after weaning, but little is known of how and why certain commensals induce these systemic commensal responses. Our preliminary data suggest that there is a limited window in early life, in which live commensal bacteria can be found in the mesenteric lymph nodes, and that these bacteria that translocate in early life induce systemic IgG responses that is specific for the same commensal bacteria. Studying the interplay between microbial translocation, humoral response to commensal bacteria, and colonization dynamics, will enhance our understanding of how early life microbes drive immune system development.