About InVivoMAb anti-mouse CD200 (OX2)
The OX-90 monoclonal antibody reacts with mouse CD200 also known as OX2. CD200 is a type 1 membrane glycoprotein belonging to the immunoglobulin superfamily. CD200 expression is limited to thymocytes, neurons, B cells, splenic follicular dendritic cells and endothelium, and subsets of T cells and dendritic cells. CD200 has been shown to co-stimulate T cell proliferation. It is thought that engagement of CD200 with its receptor, CD200R, results in inhibition and/or downregulation of myeloid cell activity. Blocking this interaction decreases the inhibitory thresholds of myeloid cells resulting in increased immune activity. The OX-90 antibody has been reported to block the binding of CD200 to CD200R in vivo.
InVivoMAb anti-mouse CD200 (OX2) Specifications
|Isotype||Rat IgG2a, κ|
|Recommended Isotype Control(s)|
|Recommended Dilution Buffer|
|Immunogen||Fusion protein consisting of mouse CD200 (extracellular region) and rat CD4 (domains 3 and 4)|
|Sterility||0.2 μm filtration|
|Production||Purified from tissue culture supernatant in an animal free facility|
|Molecular Weight||150 kDa|
|Storage||The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.|
InVivoMAb anti-mouse CD200 (OX2)
Seeds, R. E., et al. (2011). “The role of myeloid receptors on murine plasmacytoid dendritic cells in induction of type I interferon.” Int Immunopharmacol 11(7): 794-801. PubMed
This study tested the hypothesis that a set of predominantly myeloid restricted receptors (F4/80, CD36, Dectin-1, CD200 receptor and mannan binding lectins) and the broadly expressed CD200 played a role in a key function of plasmacytoid DC (pDC), virally induced type I interferon (IFN) production. The Dectin-1 ligands zymosan, glucan phosphate and the anti-Dectin-1 monoclonal antibody (mAb) 2A11 had no effect on influenza virus induced IFNalpha/beta production by murine splenic pDC. However, mannan, a broad blocking reagent against mannose specific receptors, inhibited IFNalpha/beta production by pDC in response to inactivated influenza virus. Moreover, viral glycoproteins (influenza virus haemagglutinin and HIV-1 gp120) stimulated IFNalpha/beta production by splenocytes in a mannan-inhibitable manner, implicating the function of a lectin in glycoprotein induced IFN production. Lastly, the effect of CD200 on IFN induction was investigated. CD200 knock-out macrophages produced more IFNalpha than wild-type macrophages in response to polyI:C, a MyD88-independent stimulus, consistent with CD200’s known inhibitory effect on myeloid cells. In contrast, blocking CD200 with an anti-CD200 mAb resulted in reduced IFNalpha production by pDC-containing splenocytes in response to CpG and influenza virus (MyD88-dependent stimuli). This suggests there could be a differential effect of CD200 on MyD88 dependent and independent IFN induction pathways in pDC and macrophages. This study supports the hypothesis that a mannan-inhibitable lectin and CD200 are involved in virally induced type I IFN induction.
Koning, N., et al. (2009). “Distribution of the immune inhibitory molecules CD200 and CD200R in the normal central nervous system and multiple sclerosis lesions suggests neuron-glia and glia-glia interactions.” J Neuropathol Exp Neurol 68(2): 159-167. PubMed
CD200 is a membrane glycoprotein that suppresses immune activity via its receptor, CD200R. CD200-CD200R interactions have recently been considered to contribute to the “immune privileged” status of the central nervous system (CNS). The mechanisms by which these interactions take place are not well understood in part because there is limited detailed information on the distribution of CD200 and CD200R in the CNS. Here, we used immunohistochemistry to characterize the distinct anatomical and cellular distribution of these molecules in multiple sclerosis (MS) lesions and controls. CD200 was robustly expressed in gray matter areas including the cerebral cortex, hippocampus, striatum, cerebellum, and spinal cord, where neurons appeared immunopositive. CD200 expression was also detected in oligodendrocytes, but not in astrocytes or microglia. In CNS samples from MS patients, CD200 expression was additionally observed on reactive astrocytes in chronic active plaque centers, despite our previous finding of an overall decrease ofCD200 expression in MS lesions. In contrast to CD200, the immunolocalization pattern of CD200R was very distinct, showing high expression on perivascular macrophages in both gray and white matter. Using flow cytometry, we also found that human primary microglia express low levels of CD200R. These data suggest that CD200-mediated immune suppression may occur not only via neuron-microglia interactions, but also via glia-glia interactions, especially in inflammatory conditions in which an immune-suppressive environment needs to be restored; this may occur as a result of increased CD200 expression on reactive astrocytes.
Snelgrove, R. J., et al. (2008). “A critical function for CD200 in lung immune homeostasis and the severity of influenza infection.” Nat Immunol 9(9): 1074-1083. PubMed
The lung must maintain a high threshold of immune ‘ignorance’ to innocuous antigens to avoid inflammatory disease that depends on the balance of positive inflammatory signals and repressor pathways. We demonstrate here that airway macrophages had higher expression of the negative regulator CD200 receptor (CD200R) than did their systemic counterparts. Lung macrophages were restrained by CD200 expressed on airway epithelium. Mice lacking CD200 had more macrophage activity and enhanced sensitivity to influenza infection, which led to delayed resolution of inflammation and, ultimately, death. The administration of agonists that bind CD200R, however, prevented inflammatory lung disease. Thus, CD200R is critical for lung macrophage immune homeostasis in the resting state and limits inflammatory amplitude and duration during pulmonary influenza infection.
Zhang, S., et al. (2004). “Molecular mechanisms of CD200 inhibition of mast cell activation.” J Immunol 173(11): 6786-6793. PubMed
CD200 and its receptor CD200R are both type I membrane glycoproteins that contain two Ig-like domains. Engagement of CD200R by CD200 inhibits activation of myeloid cells. Unlike the majority of immune inhibitory receptors, CD200R lacks an ITIM in the cytoplasmic domain. The molecular mechanism of CD200R inhibition of myeloid cell activation is unknown. In this study, we examined the CD200R signaling pathways that control degranulation of mouse bone marrow-derived mast cells. We found that upon ligand binding, CD200R is phosphorylated on tyrosine and subsequently binds to adapter proteins Dok1 and Dok2. Upon phosphorylation, Dok1 binds to SHIP and both Dok1 and Dok2 recruit RasGAP, which mediates the inhibition of the Ras/MAPK pathways. Activation of ERK, JNK, and p38 MAPK are all inhibited by CD200R engagement. The reduced activation of these MAPKs is responsible for the observed inhibition of mast cell degranulation and cytokine production. Similar signaling events were also observed upon CD200R engagement in mouse peritoneal cells. These data define a novel inhibitory pathway used by CD200R in modulating mast cell function and help to explain how engagement of this receptor in vivo regulates myeloid cell function.
Hoek, R. M., et al. (2000). “Down-regulation of the macrophage lineage through interaction with OX2 (CD200).” Science 290(5497): 1768-1771. PubMed
OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, 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 (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.