The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

Research output: Contribution to journalArticle

Abstract

The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE(+) cells in memory responses is particularly unclear. IgE(+) B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE(+) GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE(+) GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE(+) GC cells, whereas sequential switching gives rise to IgE(+) PCs. We propose a comprehensive model for the generation and memory of IgE responses.

Details

Authors
  • Jin-Shu He
  • Michael Meyer-Hermann
  • Deng Xiangying
  • Lim Yok Zuan
  • Leigh Ann Jones
  • Lakshmi Ramakrishna
  • Victor C de Vries
  • Jayashree Dolpady
  • Hoi Aina
  • Sabrina Joseph
  • Sriram Narayanan
  • Sharrada Subramaniam
  • Manoj Puthia
  • Glenn Wong
  • Huizhong Xiong
  • Michael Poidinger
  • Joseph F Urban
  • Juan J Lafaille
  • Maria A Curotto de Lafaille
External organisations
  • A*STAR Singapore Immunology Network (SIgN)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Animals, Apoptosis, B-Lymphocytes/cytology, Cell Differentiation, Germinal Center/cytology, Green Fluorescent Proteins/genetics, Immunoglobulin Class Switching, Immunoglobulin E/metabolism, Immunoglobulin G/metabolism, Immunologic Memory, Mice, Mice, Inbred BALB C, Mice, Transgenic, Models, Immunological, Nippostrongylus, Plasma Cells/cytology, Receptors, Antigen, B-Cell/metabolism, Signal Transduction, Strongylida Infections/immunology
Original languageEnglish
Pages (from-to)2755-2771
JournalJournal of Experimental Medicine
Volume210
Issue number12
Publication statusPublished - 2013 Nov 18
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes