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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.

Original publication

DOI

10.1084/jem.20131539

Type

Journal

The Journal of experimental medicine

Publication Date

11/11/2013

Volume

210

Pages

2755 - 2771

Addresses

Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore 138648.

Keywords

Germinal Center, B-Lymphocytes, Plasma Cells, Animals, Mice, Inbred BALB C, Mice, Transgenic, Mice, Nippostrongylus, Strongylida Infections, Immunoglobulin E, Immunoglobulin G, Green Fluorescent Proteins, Receptors, Antigen, B-Cell, Signal Transduction, Apoptosis, Cell Differentiation, Immunoglobulin Class Switching, Immunologic Memory, Models, Immunological