Decreased expression of CD200R3 on mouse basophils as a novel marker for IgG1-mediated anaphylaxis

IgE-mediated mast cell activation is the trigger of anaphylaxisin humans, whereas it is known that not only IgE but also IgG can induce anaphylaxisin mice. In our preliminary experiments, the expression of a murine basophilidentification marker, CD200R3, on antigen-sensitized basophilsdecreased following specific antigen challenge. Interestingly, this decrease did not always correspond with increased expression of the IgE-mediated basophil activationmarker CD200R1. Since IgG as well as IgE plays a role in mouse anaphylaxis, we hypothesized that the observed decrease in CD200R3 on basophilswas caused by IgG-mediated cell activation. We attempted to establish whether CD200R3 is a marker of IgG-mediated basophil activationand if its expression is correlated with anaphylaxisin a mouse model. Mouse basophilswere stimulated via Fc∊Rs and/or FcγRs, and levels of CD200R1 and CD200R3 were analyzed by flow cytometry. Basophilsderived from naive mice were challenged with a natural antigen, β- lactoglobulin, after passive sensitization with anti-β-LG serum or IgG/IgG subclass-depleted antiserum. Systemic anaphylaxiswas induced by i.v. injection of anti-FcγRIII/II monoclonal antibody, and CD200R3 expression on peripheral basophilswas assessed. Stimulation via Fc∊Rs induced a significant increase in CD200R1 expression but had only a small effect on that of CD200R3. However, anti-FcγRIII/II stimulation reduced CD200R3 expression markedly. In passive sensitization experiments, down-regulation of CD200R3 induced by antigen challenge was strongly negated by the depletion of IgG or IgG1 from antiserum. Intravenous injection of anti-FcγRIII/II induced CD200R3 down-regulation on peripheral basophils, together with a drop in rectal temperature. Lowered CD200R3 expression on basophilsis induced by IgG-mediated stimulation via FcγRs. Use of CD200R1 and CD200R3 as activation markers enables the evaluation of murine basophil activationmediated by IgE and IgG, respectively.