title: Autonomous membrane IgE signaling prevents IgE-memory formation.
abstract: Aberrant production of IgE antibodies can lead to allergic diseases. Normally, IgE(+) B cells rarely differentiate into memory B cells (Bmem) or long-lived plasma cells (LLPCs), as they only transiently participate in the germinal center (GC), but the mechanism behind this remains elusive. We found that membrane IgE (mIgE) autonomously triggered rapid plasma-cell differentiation and apoptosis independently of antigen or cellular context, predominantly through the mutually independent CD19-PI3K-Akt-IRF4 and BLNK-Jnk/p38 pathways, respectively, and we identified the ectodomains of mIgE as being responsible. Accordingly, deregulated GC IgE(+) B cell proliferation and prolonged IgE production with exaggerated anaphylaxis were observed in CD19- and BLNK-deficient mice. Our findings reveal an autonomous mIgE signaling mechanism that normally prevents IgE(+) Bmem and LLPC formation, providing insights into the molecular pathogenesis of allergic diseases.
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Haniuda
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Fukao
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Kodama
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Division of Molecular Biology, Research Institute for Biomedical Sciences, Tokyo University of Science, Noda, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kitamura
mesh_terms: D016475:3T3 Cells; D000707:Anaphylaxis / Q000276:immunology*; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics; D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology*; D020013:Calcium Signaling; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D058501:Enzyme-Linked Immunospot Assay; D018858:Germinal Center / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology*; D017578:Immunoglobulin Class Switching; D007073:Immunoglobulin E / Q000378:metabolism*; D007074:Immunoglobulin G / Q000378:metabolism; D007156:Immunologic Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010950:Plasma Cells / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D007074:Immunoglobulin G; D011947:Receptors, Antigen, B-Cell; D007073:Immunoglobulin E