CD200 (OX-2) is a 45 kD cell surface glycoprotein that belongs to the immunoglobulin superfamily (IgSF). CD200 is composed of 202 amino acid extracellular domain containing two IgSF domains, 27 amino acid transmembrane segment, and a 19 amino acid cytoplasmic domain. CD200 is the only known ligand of the CD200R family and it is highly conserved in the CNS, expressed mainly by neurons and vascular endothelium.? It is also present in most peripheral cell types, thymocytes, T and B cells, and dendritic cells. CD200 and CD200R interact with each other through N-terminal IgSF domains. Their interaction plays important roles in negatively regulating immune responses, and attenuating autoimmune diseases and excessive inflammatory responses against pathogens. High expression of CD200 in CNS is thought to be a mechanism of constitutive immune suppression, and is developmentally regulated in the mouse brain. Deficiency in neuronal CD200 may explain the chronic inflammation in human neurodegenerative diseases such as Alzheimer, Parkinson, and multiple sclerosis. CD200 and CD200R interaction has also been shown to play an important role in the regulation of anti-tumor immunity, and overexpression of CD200 has been reported in a number of malignancies, including CLL, as well as on cancer stem cells.