ABSTRACT
DC-LAMP, a member of the lysosomal-associated membrane protein (LAMP) family, is specifically expressed by human dendritic cells (DC) upon activation and therefore serves as marker of human DC maturation. DC-LAMP is detected first in activated human DC within MHC class II molecules-containing compartments just before the translocation of MHC class II-peptide complexes to the cell surface, suggesting a possible involvement in this process. The present study describes the cloning and characterization of mouse DC-LAMP, whose predicted protein sequence is over 50% identical to the human counterpart. The mouse DC-LAMP gene spans over 25 kb and shares syntenic chromosomal localization (16B2-B4 and 3q26) and conserved organization with the human DC-LAMP gene. Analysis of mouse DC-LAMP mRNA and protein revealed the expression in lung peripheral cells, but also its unexpected absence from mouse lymphoid organs and from mouse DC activated either in vitro or in vivo. In conclusion, mouse DC-LAMP is not a marker of mature mouse DC and this observation raises new questions regarding the role of human DC-LAMP in human DC.
Subject(s)
Antigens, CD/genetics , Cloning, Molecular , Dendritic Cells/metabolism , Animals , Antigens, CD/metabolism , Base Sequence , Cell Differentiation/genetics , Cell Differentiation/physiology , Humans , Lung/metabolism , Lysosomal Membrane Proteins , Mice , Molecular Sequence Data , Organ Specificity/physiology , Phylogeny , RNA, Messenger/metabolism , Sequence AlignmentABSTRACT
Recent studies in humans have highlighted the importance of a distinct cellular entity, the plasmacytoid dendritic cell (PDC). To identify genes for which expression is restricted to human PDCs, a cDNA subtraction technique was applied using cDNA from activated monocyte-derived DCs (MDDCs) as competitor. In the 650 sequences analyzed, 25% were for B-cell transcripts. We also found lymphoid-related genes, immunoglobulinlike transcript 7 (ILT7), granzyme B (GrB), Spi-B, and the receptor tyrosine kinase Eph-B1. Granzyme B was up-regulated on activation, and protein was detected only in PDCs. Eph-B1 protein was expressed in the cytoplasm and the nuclei of PDCs and MDDCs, respectively. Interestingly, several novel molecules have been identified that were predicted to encode for a type 2 transmembrane protein (BRI(3)), a putative cytokine (C-15, a cysteine-rich-secreted protein), and a type 1 leucine-rich repeat protein (MAPA). The identification of genes expressed in PDCs provides new insights into their function and origin.
