Alternative titles; symbols
HGNC Approved Gene Symbol: CD200
Cytogenetic location: 3q13.2 Genomic coordinates (GRCh38): 3:112,332,573-112,362,812 (from NCBI)
McCaughan et al. (1987) stated that the MRC OX-2 antigen was defined by a mouse monoclonal antibody raised against rat thymocyte membrane glycoproteins. The MRC OX-2 antigens purified from thymocytes and brain are glycoproteins of a molecular mass of 47,000 and 41,000 daltons containing 33% and 24% carbohydrate, respectively. Protein and cDNA sequencing showed that these antigens contain 248 amino acids, of which 202 are likely to be outside the cell, with a single transmembrane sequence and 19 residues on the cytoplasmic side. The extracellular part contains 2 domains with sequence similarities to immunoglobulin domains, establishing MRC OX-2 as a member of the immunoglobulin superfamily. McCaughan et al. (1987) isolated a genomic clone for human OX-2.
By flow cytometric analysis, Wright et al. (2001) showed that MOX2 was expressed on a subset of T cells and on all CD19 (107265)-positive B cells, and that it was upregulated on most activated T cells. Immunohistochemistry demonstrated MOX2 expression in tonsil and splenic follicular dendritic cells, with undetectable expression on B cells, low expression in thymic medulla, which was greater than in thymic cortex, and high expression on central and peripheral nerve tissue. Wright et al. (2001) concluded that MOX2 is expressed broadly and may regulate myeloid cell activity in a variety of tissues.
Cui et al. (2007) found that the expression of Cd200 was potently induced in mouse macrophages at the onset of fusion. Cd200 -/- osteoclasts had defects in multinucleation and in signaling downstream of receptor activator of NF-kappa-B (RANK, or TNFRSF11A; 603499), both of which are essential for osteoclastogenesis. Cd200 -/- mice had a lower number of osteoclasts and a higher bone density than wildtype mice. Cui et al. (2007) concluded that CD200-CD200R signaling plays a central role in macrophage fusion and osteoclast formation.
McCaughan et al. (1987) assigned the human MRC OX-2 gene to chromosome 3 using a panel of human-hamster hybrids of known karyotype. Douglas et al. (1988) described an EcoRI RFLP and narrowed the chromosomal location to 3q12-q13 by in situ hybridization. (Although Douglas et al. (1988) stated that the RFLP resided in 'MOX-1,' Barclay (1989) confirmed that in fact it resides in MOX2.)
Hoek et al. (2000) generated mice lacking Cd200 (Mox2) by a targeted disruption. In Cd200 -/- mice, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged Cd200-deficient neurons elicited an accelerated microglial response. Lack of Cd200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis. Outside the brain, disruption of Cd200-Cd200 receptor interaction precipitated susceptibility to collagen-induced arthritis in mice normally resistant to this disease. Thus, Hoek et al. (2000) concluded that in diverse tissues MOX2 delivers an inhibitory signal for the macrophage lineage.
Rygiel et al. (2009) found that Cd200 -/- mice challenged with influenza virus developed more severe disease, which was associated with increased lung infiltration and lung endothelium damage, compared with wildtype controls. Cd200 -/- mice did develop immune responses that could control viral load, suggesting that the severe disease was caused by an exaggerated immune response. Disease could be prevented by T-cell depletion before viral challenge, despite the dramatically increased viral load that resulted. Rygiel et al. (2009) concluded that T cells are essential for the manifestation of disease symptoms during influenza infection, and that lack of downmodulating CD200-CD200R signaling, rather than viral load, increases immune pathology.
Barclay, A. N. Personal Communication. Oxford, England 1/9/1989.
Cui, W., Cuartas, E., Ke, J., Zhang, Q., Einarsson, H. B., Sedgwick, J. D., Li, J., Vignery, A. CD200 and its receptor, CD200R, modulate bone mass via the differentiation of osteoclasts. Proc. Nat. Acad. Sci. 104: 14436-14441, 2007. [PubMed: 17726108] [Full Text: https://doi.org/10.1073/pnas.0702811104]
Douglas, J., Albertson, D. G., Barclay, A. N., Davis, M., Rabbitts, P. H. RFLP and mapping of human MOX-1 gene on chromosome 3. Nucleic Acids Res. 16: 9067 only, 1988. [PubMed: 2902568] [Full Text: https://doi.org/10.1093/nar/16.18.9067]
Hoek, R. M., Ruuls, S. R., Murphy, C. A., Wright, G. J., Goddard, R., Zurawski, S. M., Blom, B., Homola, M. E., Streit, W. J., Brown, M. H., Barclay, A. N., Sedgwick, J. D. Down-regulation of the macrophage lineage through interaction with OX2 (CD200). Science 290: 1768-1771, 2000. [PubMed: 11099416] [Full Text: https://doi.org/10.1126/science.290.5497.1768]
McCaughan, G. W., Clark, M. J., Barclay, A. N. Characterization of the human homolog of the rat MRC OX-2 membrane glycoprotein. Immunogenetics 25: 329-335, 1987. [PubMed: 3032785] [Full Text: https://doi.org/10.1007/BF00404426]
McCaughan, G. W., Clark, M. J., Hurst, J., Grosveld, F., Barclay, A. N. The gene for MRC OX-2 membrane glycoprotein is localized on human chromosome 3. Immunogenetics 25: 133-135, 1987. [PubMed: 3817906] [Full Text: https://doi.org/10.1007/BF00364281]
Rygiel, T. P., Rijkers, E. S. K., de Ruiter, T., Stolte, E. H., van der Valk, M., Rimmelzwaan, G. F., Boon, L., van Loon, A. M., Coenjaerts, F. E., Hoek, R. M., Tesselaar, K., Meyaard, L. Lack of CD200 enhances pathological T cell responses during influenza infection. J. Immun. 183: 1990-1996, 2009. [PubMed: 19587022] [Full Text: https://doi.org/10.4049/jimmunol.0900252]
Wright, G. J., Jones, M., Puklavec, M. J., Brown, M. H., Barclay, A. N. The unusual distribution of the neuronal/lymphoid cell surface CD200 (OX2) glycoprotein is conserved in humans. Immunology 102: 173-179, 2001. [PubMed: 11260322] [Full Text: https://doi.org/10.1046/j.1365-2567.2001.01163.x]