Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 210, Issue 12, Pages 2755-2771Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20131539
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Funding
- Bundesministeriums fur Bildung und Forschung GerontoSys initiative
- Human Frontier Science Program
- SIgN-A*STAR core fund
- B. Levine scholarship
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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.
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