Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin.
The developmental origin of type I interferon (IFN)-producing plasmacytoid dendritic cells (PDCs) is controversial. In particular, the rearrangement of immunoglobulin heavy chain (IgH) genes in murine PDCs and the expression of pre-T cell receptor alpha (pTalpha) gene by human PDCs were proposed as evidence for their "lymphoid" origin. Here we demonstrate that PDCs capable of IFN production develop efficiently from both myeloid- and lymphoid-committed progenitors. Rearranged IgH genes as well as RAG transcripts were found in both myeloid- and lymphoid-derived PDCs. The human pTalpha transgenic reporter was activated in both myeloid- and lymphoid-derived PDCs at a level comparable to pre-T cells. PDCs were the only cell population that activated murine RAG1 knockin and human pTalpha transgenic reporters outside the lymphoid lineage. These results highlight a unique developmental program of PDCs that distinguishes them from other cell types including conventional dendritic cells.
Shigematsu
Hirokazu
H
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Reizis
Boris
B
Iwasaki
Hiromi
H
Mizuno
Shin-ichi
S
Hu
Dan
D
Traver
David
D
Leder
Philip
P
Sakaguchi
Nobuo
N
Akashi
Koichi
K
D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D003713:Dendritic Cells / Q000502:physiology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta
D018398:Homeodomain Proteins; D007370:Interferon Type I; D008562:Membrane Glycoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; C090377:pre-T cell receptor alpha; C064658:RAG-1 protein