title: Decreased expression of CD200R3 on mouse basophils as a novel marker for IgG1-mediated anaphylaxis.
abstract: IgE-mediated mast cell activation is the trigger of anaphylaxis in humans, whereas it is known that not only IgE but also IgG can induce anaphylaxis in mice. In our preliminary experiments, the expression of a murine basophil identification marker, CD200R3, on antigen-sensitized basophils decreased following specific antigen challenge. Interestingly, this decrease did not always correspond with increased expression of the IgE-mediated basophil activation marker CD200R1. Since IgG as well as IgE plays a role in mouse anaphylaxis, we hypothesized that the observed decrease in CD200R3 on basophils was caused by IgG-mediated cell activation. We attempted to establish whether CD200R3 is a marker of IgG-mediated basophil activation and if its expression is correlated with anaphylaxis in a mouse model. Mouse basophils were stimulated via Fc∊Rs and/or FcγRs, and levels of CD200R1 and CD200R3 were analyzed by flow cytometry. Basophils derived 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 anaphylaxis was induced by i.v. injection of anti-FcγRIII/II monoclonal antibody, and CD200R3 expression on peripheral basophils was 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 basophils is induced by IgG-mediated stimulation via FcγRs. Use of CD200R1 and CD200R3 as activation markers enables the evaluation of murine basophil activation mediated by IgE and IgG, respectively.
authors.affiliation: Nutritional Science Institute, Morinaga Milk Industry Co., Ltd. Zama, Kanagawa, 252-8583, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwamoto
authors.affiliation: Nutritional Science Institute, Morinaga Milk Industry Co., Ltd. Zama, Kanagawa, 252-8583, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Nutritional Science Institute, Morinaga Milk Industry Co., Ltd. Zama, Kanagawa, 252-8583, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakazato
authors.affiliation: Nutritional Science Institute, Morinaga Milk Industry Co., Ltd. Zama, Kanagawa, 252-8583, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Namba
authors.affiliation: Nutritional Science Institute, Morinaga Milk Industry Co., Ltd. Zama, Kanagawa, 252-8583, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeda
keywords: CD200R1; CD200R3; IgG-mediated anaphylaxis; basophil activation test; mouse basophil