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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #308791
Title: The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

Author
item HE, J-S - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item MEYER-HERMANN, M - Helmholtz Centre
item XIANGYING, D - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item ZUAN, L - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item JONES, L - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item RAMAKRISHNA, L - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item DE VRIES, V - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item DOLPADY, J - New York University School Of Medicine
item AINA, H - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item JOSEPH, S - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item NARAYANAN, S - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item SUBRAMANIAM, S - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item PUTIA, M - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item WONG, G - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item XIONG, H - New York University School Of Medicine
item POIDINGER, M - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item Urban, Joseph
item LAFAILLE, J - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research
item CUROTTO DE LAFAILLE, M - Singapore Immunology Network (SIGN), Agency For Science, Technology And Research

Submitted to: Journal of Experimental Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/11/2013
Publication Date: 11/18/2013
Citation: He, J., Meyer-Hermann, M., Xiangying, D., Zuan, L.Y., Jones, L.A., Ramakrishna, L., De Vries, V.C., Dolpady, J., Aina, H., Joseph, S., Narayanan, S., Subramaniam, S., Putia, M., Wong, G., Xiong, H., Poidinger, M., Urban Jr, J.F., Lafaille, J.J., Curotto De Lafaille, M.A. 2013. The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response. Journal of Experimental Medicine. 210(12):2755-71. doi: 10.1084/jem.20131539.

Interpretive Summary: IgE antibodies play a central role in allergic reactions and responses to parasitic worm infections. The cross-linking of IgE molecules on tissue and blood cells called mast cells and basophils, respectively, leads to degranulation and release of many inflammatory molecules like histamine that are indicative of allergic disease. Thus, understanding how IgE is produced is critical to the control of these diseases. In this study, techniques were devised to study the dynamics of IgE producing cells in lymph nodes in mice. It was found that the IgE producing cells “fail to thrive” and die off rapidly in the lymph nodes which greatly limits their contribution to the memory response to allergens. Other regulatory controls were observed that directly produce IgE containing cells or give rise to these cells from cells that produce other types of antibodies. The information is important to scientists that study targets that control the production of this type of antibody in order to develop strategies to regulate the responses to allergens but enhance the protective responses to parasitic worm infection.

Technical 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 towards the plasma cell (PC) fate, and a 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+ PC. We propose a comprehensive model for the generation and memory of IgE responses.