The immune inhibitory complex CD200/CD200R is developmentally regulated in the mouse brain.
The CD200/CD200R inhibitory immune ligand-receptor system regulates microglial activation/quiescence in adult brain. Here, we investigated CD200/CD200R at different stages of postnatal development, when microglial maturation takes place. We characterized the spatiotemporal, cellular, and quantitative expression pattern of CD200 and CD200R in the developing and adult C57/BL6 mice brain by immunofluorescent labeling and Western blotting. CD200 expression increased from postnatal day 1 (P1) to P5-P7, when maximum levels were found, and decreased to adulthood. CD200 was located surrounding neuronal bodies, and very prominently in cortical layer I, where CD200(+) structures included glial fibrillary acidic protein (GFAP)(+) astrocytes until P7. In the hippocampus, CD200 was mainly observed in the hippocampal fissure, where GFAP(+) /CD200(+) astrocytes were also found until P7. CD200(+) endothelium was seen in the hippocampal fissure and cortical blood vessels, notably from P14, showing maximum vascular CD200 in adults. CD200R(+) cells were a population of ameboid/pseudopodic Iba1(+) microglia/macrophages observed at all ages, but significantly decreasing with increasing age. CD200R(+) /Iba1(+) macrophages were prominent in the pial meninges and ventricle lining, mainly at P1-P5. CD200R(+) /Iba1(+) perivascular macrophages were observed in cortical and hippocampal fissure blood vessels, showing maximum density at P7, but being prominent until adulthood. CD200R(+) /Iba1(+) ameboid microglia in the cingulum at P1-P5 were the only CD200R(+) cells in the nervous tissue. In conclusion, the main sites of CD200/CD200R interaction seem to include the molecular layer and pial surface in neonates and blood vessels from P7 until adulthood, highlighting the possible role of the CD200/CD200R system in microglial development and renewal.
Medical Histology, Institute of Neuroscience, Department of Cell Biology, Physiology, and Immunology, Universitat Autonoma Barcelona, Bellaterra 08193, Barcelona, Spain. kalpana.shrivastava@uab.cat
Kalpana
K
Shrivastava
Pau
P
Gonzalez
Laia
L
Acarin
D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D000918:Antibody Specificity / Q000235:genetics; D000937:Antigen-Antibody Reactions / Q000235:genetics; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism*; D001923:Brain Chemistry / Q000235:genetics / Q000276:immunology*; D005260:Female; D006624:Hippocampus / Q000098:blood supply / Q000254:growth & development / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019579:Neocortex / Q000098:blood supply / Q000254:growth & development / Q000276:immunology; D009433:Neural Inhibition / Q000235:genetics / Q000276:immunology*; D055495:Neurogenesis / Q000235:genetics / Q000276:immunology
D015703:Antigens, CD; C492346:CD200 receptor, mouse; D008562:Membrane Glycoproteins; C042739:antigens, CD200