Immature monocytes acquire antigens from other cells in the bone marrow and present them to T cells after maturing in the periphery.
Monocytes are circulating precursors for tissue macrophages and dendritic cells (DCs) but are not recognized to directly participate in antigen presentation. We developed techniques to label mouse monocyte subsets with particulate tracers in vivo. Gr-1lo but not Gr-1hi monocytes were stably labeled by intravenous injection of 0.5-microm microspheres. Gr-1hi monocytes could be labeled when the microspheres were injected after systemic depletion of blood monocytes and spleen macrophages. In this condition, the phagocytic tracer was transferred to immature bone marrow monocytes by neutrophils and B cells that first carried the particles to the bone marrow. Moreover, antigens from B cells or proteins conjugated to the tracer particles were processed for presentation by monocytes and could induce T cell responses in the periphery. Cell-associated antigen taken up by bone marrow monocytes was retained intracellularly for presentation of the antigen days later when monocyte-derived DCs migrated to lymph nodes or in vitro after differentiation with granulocyte/macrophage colony-stimulating factor. These data reveal that immature monocytes unexpectedly sample antigen from the bone marrow environment and that they can present these antigens after they leave the bone marrow.
Department of Gene and Cell Medicine, Icahn Research Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
Frank
F
Tacke
Florent
F
Ginhoux
Claudia
C
Jakubzick
Nico
N
van Rooijen
Miriam
M
Merad
Gwendalyn J
GJ
Randolph
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D047589:Leukocyte Reduction Procedures / Q000379:methods; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008863:Microspheres; D009000:Monocytes / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D019707:Receptors, Chemokine / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
C503133:Gr-1 protein, mouse; D019707:Receptors, Chemokine