RRC ID 47451
Author Haniuda K, Fukao S, Kodama T, Hasegawa H, Kitamura D.
Title Autonomous membrane IgE signaling prevents IgE-memory formation.
Journal Nat. Immunol.
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.
Volume 17(9)
Pages 1109-17
Published 2016-9
DOI 10.1038/ni.3508
PII ni.3508
PMID 27428827
MeSH 3T3 Cells Anaphylaxis / immunology* Animals Antigens, CD19 / genetics Apoptosis B-Lymphocytes / physiology* Calcium Signaling Cell Differentiation Cell Membrane* / metabolism Cell Proliferation Enzyme-Linked Immunospot Assay Germinal Center / immunology* Hypersensitivity / immunology* Immunoglobulin Class Switching Immunoglobulin E / metabolism* Immunoglobulin G / metabolism Immunologic Memory* Mice Mice, Inbred C57BL Mice, Knockout Plasma Cells / physiology* Receptors, Antigen, B-Cell / metabolism
IF 21.809
Times Cited 4
WOS Category IMMUNOLOGY
Resource
DNA material pMXs-IRES-GFP_IgM (RDB14501) pMXs-IRES-GFP_IgD (RDB14502) pMXs-IRES-GFP_IgG3 (RDB14503) pMXs-IRES-GFP_IgG1 (RDB14504) pMXs-IRES-GFP_IgG2b (RDB14505) pMXs-IRES-GFP_IgG2c (RDB14506) pMXs-IRES-GFP_IgA (RDB14507) pMXs-IRES-GFP_IgE (RDB14508) pMXs-IRES-mCherry_IgG1 (RDB14509) pMXs-IRES-mCherry_IgE (RDB14510) pMXs-IRES-GFP_CD19 (RDB14511) pMXs-IRES-GFP_CD19-2YF (RDB14512) pMXs-IRES-hNGFR_G-CaMP6 (RDB14513) pMXs-IRES-GFP_CA-Akt(E40K) (RDB14514)
Human and Animal Cells BALB/3T3 clone A31(RCB0005)