Mouse lymphoid tissue contains distinct subsets of langerin/CD207 dendritic cells, only one of which represents epidermal-derived Langerhans cells.

Langerin/CD207 is a C-type lectin associated with formation of Birbeck granules (BG) in Langerhans cells (LC). Here, we describe a monoclonal antibody (mAb 205C1) recognizing the extracellular domain of mouse langerin. Cell-surface langerin was detected in all epidermal LC, which presented a uniform phenotype. Two subpopulations of langerin + cells were identified in peripheral lymph nodes (LN). One population (subset 1) was CD11c low/+ /CD8α −/low /CD11b + /CD40 + /CD86 + . The other population (subset 2) was CD11c high /CD8α + /CD11b low , and lacked CD40 and CD86. Only subset 1 was fluorescein 5-isothiocyanate (FITC + ) following painting onto epidermis, and the appearance of such FITC + cells in draining LN was inhibited by pertussis toxin. Mesenteric LN, spleen, and thymus contained only a single population of langerin + DC, corresponding to peripheral LN subset 2. Unexpectedly, BG were absent from spleen CD8α + DC despite expression of langerin, and these organelles were not induced by mAb 205C1. Collectively, we demonstrate that two langerin + DC populations (subsets 1 and 2) co-exist in mouse lymphoid tissue. Subset 1 unequivocally identifies epidermal LC-derived DC. The distribution of subset 2 indicates a non-LC origin of these langerin + cells. These findings should facilitate our understanding of the role played by langerin in lymphoid organ DC subsets.