The development of humoral immunity to common dietary antigens in human infants is accompanied by the accumulation of specific plasma cells in the thymus

Abstract

Abstract We have reported on the accumulation of plasma cells (PCs) in the human thymus, starting several months after birth. This thymic PC niche includes clones specific to common viruses and vaccination antigens presumably generated through peripheral responses. Humans acquire humoral immunity to dietary antigens during the first 3 years of life. Here we investigated whether such immunity also resulted in the homing of specific PC to the thymus. Using a combination of dietary antigen microarrays, ELISA and ELISPOT assays, we tested for the presence of serum IgG and thymic antibody-producing cells specific to common food antigens in discarded blood and thymus specimens from 1 day to 2 year-old subjects (N=20). Our studies first confirmed cow’s milk proteins, including casein and lactoferrin, as prevalent targets of humoral responses during infancy. Remarkably, subjects with the highest serum IgG titer to cow’s milk antigens also had high-frequency PC in the thymus specific to the same antigens. Our study demonstrates for the first time the presence of antibody-secreting cells specific to dietary antigens in the thymic of human infants. Their possible contribution to tolerance mechanisms warrants further investigation. This work was supported by a NIH-NIAID grant U01-AI131339. Dietary antigen arrays (ImmunoCap) used in this study were a gift from Thermo Fisher Scientific.