Developmental kinetics and lifespan of dendritic cells in mouse lymphoid organs

Abstract

The labeling kinetics of 5 dendritic cell (DC) subtypes within the lymphoid organs of healthy laboratory mice during continuous administration of bromodeoxyuridine (BrdU) was determined to investigate developmental relationships and determine turnover rates. Individual DC subtypes behaved as products of separate developmental streams, at least as far back as their dividing precursors. The rate of labeling varied with the lymphoid organ and the DC subtype. Labeling was faster overall in spleen and mesenteric lymph nodes (LNs) and slower in thymus and skin-draining LNs. The CD8+ DC subtype displayed the most rapid turnover, with a uniformly short (3-day) lifespan in spleen but with distinct short-lived and longer-lived subgroups in thymus. All the skin-derived DCs in LNs showed delayed and slow BrdU labeling, indicating a long overall lifespan; however, this was shown to reflect a long residence time in skin rather than a long-duration presenting antigen in the draining LN. Epidermal-derived Langerhans DCs displayed longer BrdU labeling lag and slower overall turnover than the dermal-derived DCs, and the movement of fluorescent Langerhans DC from skin to LN was slower than that of dermal DCs following skin painting with a fluorescent dye. However, once they arrived in lymphoid organs, all DCs present in healthy, uninfected mice displayed a rapid turnover, and this turnover was even faster after antigenic or microbial product stimulation.