Early Life Development of Bronchial Associated Lymphoid Tissue Containing Germinal Center in the Human Lung

Abstract

Abstract Early life susceptibility to respiratory pathogens is well established in infants and young children, however the specific adaptations of the infant immune system for responding to multiple respiratory challenges are not known. Here, we examined lung and lung-associated lymph nodes derived from infant and pediatric organ donors (0–13 years) by confocal immunofluorescence and high dimensional flow cytometry. We identified early formation of bronchial associated lymphoid tissue (BALT) where active immune responses are initiated. At 8 days of life, few immune cells were present around the airways. By 5 months old, we start to observe BALT formation. However, BALT lose their structure with aging and are mostly absent by 10 years of age with CD4 memory T cells dominating the population around the central airways. Germinal centers are seen in 50–60% of BALT during the first two years of life. The percentage of BALT with germinal centers decreases over age, while germinal center formation in lung lymph nodes is maintained throughout infancy and childhood. Flow cytometry data shows seeding of transitional and immature B cells in the lung during infancy, which decreases over age. However, proportion of IgG and IgA memory B cells increases significantly over age both in the lung and lung lymph nodes. The frequency of naïve B cells is stable throughout childhood in both sites. Our results suggest that localized tertiary lymphoid structures in pediatric lungs may be an important mechanism for mobilizing rapid in situ protection during the first few years of life when memory T cells and B cells are not fully established. Supported by grants listed below: “Human Atlas of Neonatal Development and Early Life-Immunity (HANDEL-I)”(award Number 2018PG-T1D071 The Leona M. and Harry B. Helmsley Charitable Trust) “Immunobiology and alveolar physiology of the aging lung” (U01 HL145547, NIH/NHLBI )