Development of a Novel IgG1 Anaphylaxis Mouse Model with Uniquely Characteristic Skin Manifestations Induced Through the FcγRIII-Histamine Pathway.

BACKGROUND: Studies of passive anaphylaxis, in which mouse immunoglobulin G (IgG) and its antigens are administered to mice, believe that platelet-activating factor (PAF) is more important than histamine and that basophils or macrophages are primarily involved. However, the full extent of IgG-dependent anaphylaxis is still unclear; that is, little agreement has been reached about the mechanism. METHODS: First, we established the novel model of IgG1 anaphylaxis induced by the intravenous administration of two types of IgG1 and a fluorescent dye-labeled antigen, as IgG1 immune complex in HR-1 hairless mice. Subsequently, pharmacological analysis was used to investigate the underlying mechanisms of IgG1 anaphylaxis in this established model. RESULTS: The novel IgG1 anaphylaxis model can induce the IgG-induced Anaphylaxis-dependent Spotted Distribution of fluorescently labeled Immune complexes in the Skin, named "G-ASDIS". Moreover, this model was triggered primarily by the FcγRIII-dependent histamine release, which is different from the conventional model in which PAF was involved in the development of IgG1 anaphylaxis. Basophils in the circulation and mast cells in the skin may participate in the development of IgG1 anaphylaxis and increased G-ASDIS. CONCLUSION: Our results propose that the novel axis, namely the FcγRIII-basophils and/or mast cell-histamine pathway, is important for IgG1 anaphylaxis. Further analysis of our model in addition to other models will lead to a broader analysis and understanding of the IgG1 anaphylaxis mechanism.

Immunoglobulin a suppresses B cell receptor-mediated activation of mouse B cells with differential inhibition of signaling molecules.

CONTEXT: We previously reported that monoclonal mouse immunoglobulin (Ig) A, OA-4, attenuates sensitization in mice by suppressing B cell activation. OBJECTIVE: Here, it is demonstrated for the first time that mouse IgA inhibits mouse B cell activation in vitro under natural conditions (i.e. in the absence of chemical, physical, and genetic modifications of IgA and B cells). MATERIALS AND METHODS: Mouse splenocytes were stimulated with anti-B cell receptor (BCR) antibody or lipopolysaccharide (LPS) in the presence or absence of OA-4. Splenic B cell proliferation and the activation of several intracellular signaling molecules were measured. RESULTS: Anti-BCR antibody-induced proliferation was markedly inhibited by OA-4 or the commercially available mouse IgA S107, whereas LPS-induced proliferation was weakly attenuated by a high concentration of OA-4. Moreover, OA-4 markedly decreased the anti-BCR antibody-induced phosphorylation of p44/42 mitogen-activated protein kinase (ERK) and CD22 and decreased phosphorylated phospholipase (PLC) γ2 and intracellular Ca2+ levels moderately, whereas protein kinase B (Akt) phosphorylation was not affected by OA-4. The MAPK/ERK kinase-ERK and phosphoinositide 3-kinase-Akt pathways were found to play a role in the proliferation of splenocytes induced by anti-BCR antibody based on experiments with their inhibitors. In contrast to that in splenic B cells, ERK phosphorylation induced by anti-BCR antibody in A20 cells was not inhibited by OA-4. The modulatory effects of IgA were different among the cell types and signaling pathways. CONCLUSION: IgA is a potential immunoregulatory drug utilizing new mechanisms that affect splenic B cells but not A20 lymphomas.