Increased incidence of anti-GBM disease in Fcgamma receptor 2b deficient mice, but not mice with conditional deletion of Fcgr2b on either B cells or myeloid cells alone.

2.50
Hdl Handle:
http://hdl.handle.net/10547/228775
Title:
Increased incidence of anti-GBM disease in Fcgamma receptor 2b deficient mice, but not mice with conditional deletion of Fcgr2b on either B cells or myeloid cells alone.
Authors:
Sharp, Phoebe E.H.; Martin-Ramirez, Javier; Boross, Peter; Mangsbo, Sara M.; Reynolds, John; Moss, Jill; Pusey, Charles D.; Cook, H. Terence; Tarzi, Ruth M.; Verbeek, J. Sjef
Abstract:
Fcgamma receptor 2b (Fcgr2b) is the only inhibitory Fcgamma receptor in both humans and mice, and is implicated in both antibody production and effector responses to antibody complexes. Reduced function of Fcgr2b has previously been associated with anti-glomerular basement membrane antibody (anti-GBM) disease in mice. However, the mice used had 129 genetic elements flanking the deleted Fcgr2b gene, which are known to increase susceptibility to autoimmunity. In order to confirm a role for Fcgr2b in protection from anti-GBM disease, wild type (WT) mice, mice lacking Fcgr2b on a pure C57BL/6 background, or mice lacking Fcgr2b on a C57BL/6 background with 129 flanking sequences, were immunized with the recombinant NC1 domain of alpha 3 Type IV collagen. Twenty two weeks after immunization, there was a higher incidence of crescentic glomerulonephritis, macrophage infiltration and renal dysfunction in both groups of Fcgr2b-/- mice, indicating an important role of Fcgr2b in regulating the development of anti-GBM disease, on both genetic backgrounds. In order to determine the cellular origin of the Fcgr2b-associated effect, disease was induced in mice with deficiency of Fcgr2b on either B cells alone (CD19Cre), or a subset of myeloid cells (LysozymeMCre). Neither B cell nor myeloid specific knockout mice developed crescentic glomeruonephritis with higher incidence than WT mice indicating that Fcgr2b deficiency on either B cells or a subset of myeloid cells alone is not sufficient to increase susceptibility to anti-GBM disease, but that a combination of cell types, or deficiency of Fcgr2b in a different cell type, is also required.
Affiliation:
Division of Immunity and Inflammation, Department of Medicine, Imperial College London, W12 0NN, UK.
Citation:
Increased incidence of anti-GBM disease in Fcgamma receptor 2b deficient mice, but not mice with conditional deletion of Fcgr2b on either B cells or myeloid cells alone. 2012, 50 (1-2):49-56 Mol. Immunol.
Publisher:
Elsevier
Journal:
Molecular immunology
Issue Date:
Feb-2012
URI:
http://hdl.handle.net/10547/228775
DOI:
10.1016/j.molimm.2011.12.007
PubMed ID:
22244885
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed/22244885
Type:
Article
Language:
en
ISSN:
1872-9142
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorSharp, Phoebe E.H.en_GB
dc.contributor.authorMartin-Ramirez, Javieren_GB
dc.contributor.authorBoross, Peteren_GB
dc.contributor.authorMangsbo, Sara M.en_GB
dc.contributor.authorReynolds, Johnen_GB
dc.contributor.authorMoss, Jillen_GB
dc.contributor.authorPusey, Charles D.en_GB
dc.contributor.authorCook, H. Terenceen_GB
dc.contributor.authorTarzi, Ruth M.en_GB
dc.contributor.authorVerbeek, J. Sjefen_GB
dc.date.accessioned2012-06-13T11:30:07Z-
dc.date.available2012-06-13T11:30:07Z-
dc.date.issued2012-02-
dc.identifier.citationIncreased incidence of anti-GBM disease in Fcgamma receptor 2b deficient mice, but not mice with conditional deletion of Fcgr2b on either B cells or myeloid cells alone. 2012, 50 (1-2):49-56 Mol. Immunol.en_GB
dc.identifier.issn1872-9142-
dc.identifier.pmid22244885-
dc.identifier.doi10.1016/j.molimm.2011.12.007-
dc.identifier.urihttp://hdl.handle.net/10547/228775-
dc.description.abstractFcgamma receptor 2b (Fcgr2b) is the only inhibitory Fcgamma receptor in both humans and mice, and is implicated in both antibody production and effector responses to antibody complexes. Reduced function of Fcgr2b has previously been associated with anti-glomerular basement membrane antibody (anti-GBM) disease in mice. However, the mice used had 129 genetic elements flanking the deleted Fcgr2b gene, which are known to increase susceptibility to autoimmunity. In order to confirm a role for Fcgr2b in protection from anti-GBM disease, wild type (WT) mice, mice lacking Fcgr2b on a pure C57BL/6 background, or mice lacking Fcgr2b on a C57BL/6 background with 129 flanking sequences, were immunized with the recombinant NC1 domain of alpha 3 Type IV collagen. Twenty two weeks after immunization, there was a higher incidence of crescentic glomerulonephritis, macrophage infiltration and renal dysfunction in both groups of Fcgr2b-/- mice, indicating an important role of Fcgr2b in regulating the development of anti-GBM disease, on both genetic backgrounds. In order to determine the cellular origin of the Fcgr2b-associated effect, disease was induced in mice with deficiency of Fcgr2b on either B cells alone (CD19Cre), or a subset of myeloid cells (LysozymeMCre). Neither B cell nor myeloid specific knockout mice developed crescentic glomeruonephritis with higher incidence than WT mice indicating that Fcgr2b deficiency on either B cells or a subset of myeloid cells alone is not sufficient to increase susceptibility to anti-GBM disease, but that a combination of cell types, or deficiency of Fcgr2b in a different cell type, is also required.en_GB
dc.language.isoenen
dc.publisherElsevieren_GB
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/22244885en_GB
dc.rightsArchived with thanks to Molecular immunologyen_GB
dc.subject.meshAnimals-
dc.subject.meshAnti-Glomerular Basement Membrane Disease-
dc.subject.meshAutoantigens-
dc.subject.meshB-Lymphocytes-
dc.subject.meshCollagen Type IV-
dc.subject.meshEnzyme-Linked Immunosorbent Assay-
dc.subject.meshFemale-
dc.subject.meshFlow Cytometry-
dc.subject.meshGlomerulonephritis-
dc.subject.meshImmunization-
dc.subject.meshImmunoglobulin G-
dc.subject.meshKidney-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, 129 Strain-
dc.subject.meshMice, Inbred C57BL-
dc.subject.meshMice, Knockout-
dc.subject.meshMicroscopy, Electron-
dc.subject.meshMyeloid Cells-
dc.subject.meshReceptors, IgG-
dc.titleIncreased incidence of anti-GBM disease in Fcgamma receptor 2b deficient mice, but not mice with conditional deletion of Fcgr2b on either B cells or myeloid cells alone.en
dc.typeArticleen
dc.contributor.departmentDivision of Immunity and Inflammation, Department of Medicine, Imperial College London, W12 0NN, UK.en_GB
dc.identifier.journalMolecular immunologyen_GB

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