title: Ontogeny of human IgE-expressing B cells and plasma cells.
abstract: BACKGROUND
  IgE-expressing (IgE+) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE+cells in vivo has confined their study almost entirely to mouse models.
  
  
  OBJECTIVE
  To characterize the development pathway of human IgE+PCs and to determine the ontogeny of human IgE+PCs.
  
  
  METHODS
  To generate human IgE+cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE+cells, the capacity of tonsil B-cell subsets to generate IgE+PCs and the class switching pathways involved.
  
  
  RESULTS
  We have identified three phenotypic stages of IgE+PC development pathway, namely (i) IgE+germinal centre (GC)-like B cells, (ii) IgE+PC-like 'plasmablasts' and (iii) IgE+PCs. The same phenotypic stages were also observed for IgG1+cells. Total tonsil B cells give rise to IgE+PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE+PCs, generates IgE+PCs by sequential switching. PC differentiation of IgE+cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgES), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgEL), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice.
  
  
  CONCLUSIONS
  Generation of IgE+PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL/mIgESratio may be implicated in survival of IgE+B cells during PC differentiation and allergic disease.
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: F
authors.identifier: http://orcid.org/0000-0001-8228-4868
authors.initials: F
authors.lastname: Ramadani
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: Bowen
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Upton
authors.affiliation: Division of Asthma, Allergy and Lung Biology, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: P S
authors.initials: PS
authors.lastname: Hobson
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Chan
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: J-B
authors.initials: JB
authors.lastname: Chen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: T W
authors.initials: TW
authors.lastname: Chang
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: J M
authors.initials: JM
authors.lastname: McDonnell
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Sutton
authors.affiliation: Division of Asthma, Allergy and Lung Biology, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Fear
authors.affiliation: Randall Division of Cell and Molecular Biohphysics, King's College, London, UK.|Medical Research Council and Asthma UK Centre in Allergic Mechanisms in Asthma, London, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Gould
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics / Q000276:immunology; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D016130:Immunophenotyping; D010641:Phenotype; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D007074:Immunoglobulin G; D007073:Immunoglobulin E
keywords: IgE class switching; allergy; germinal centre; human B cells; plasma cell