Abstract
Immunoglobulin E (IgE) antibodies are pathogenic in asthma and allergic diseases, but the in vivo biology of IgE-producing (IgE+) cells is poorly understood. A model of the differentiation of IgE+ B cells proposes that IgE+ cells develop through a germinal-center IgG1+ intermediate and that IgE memory resides in the compartment of IgG1+ memory B cells. Here we have used a reporter mouse expressing green fluorescent protein associated with membrane IgE transcripts (IgE-GFP) to assess in vivo IgE responses. In contrast to the IgG1-centered model of IgE switching and memory, we found that IgE+ cells developed through a germinal-center IgE+ intermediate to form IgE+ memory B cells and plasma cells. Our studies delineate a new model for the in vivo biology of IgE switching and memory.
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Acknowledgements
We thank R. Locksley (University of California, San Francisco) for larvae of N. brasiliensis; J. Cupp, R. Weimer, J.-W. Tsai, R. Noubade, J. Dunyanen, R. Ferrando and M. Larson for technical assistance; H. Qi for advice on germinal-center imaging; and F. Martin, M.Balazs, and A. Zarrin for discussions and advice.
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O.T., H.D.B., E.L. and J.G.E. designed and did experiments, and wrote the manuscript; D.Y., E.E.M.S. and M.Z. did experiments; C.D.A. designed experiments and wrote the manuscript; W.P.L. and M.X. designed experiments; and L.C.W. designed experiments, wrote the manuscript, and super vised the project.
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All authors are employed by Genentech, and D.Y., H.D.B., E.E.M.S., M.Z., E.L., W.P.L., J.G.E., C.D.A., M.X. and L.C.W. hold equity in the Roche Group.
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Supplementary Figures 1–8 (PDF 5754 kb)
Supplementary Video 1
GFP+ cells show rapid migration dynamics in the lymph node follicles of N. brasiliensis-infected IgE-GFP reporter mice. GFP+ cells (green) were visualized in an intact mesenteric lymph node by 2-photon microscopy at 13 days post-infection. The second harmonic signal (blue) identifies the collagen-rich lymph node capsule. Time shown in Hrs:Mins:Secs. Scale bar, 30μm. (MOV 1275 kb)
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Talay, O., Yan, D., Brightbill, H. et al. IgE+ memory B cells and plasma cells generated through a germinal-center pathway. Nat Immunol 13, 396–404 (2012). https://doi.org/10.1038/ni.2256
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DOI: https://doi.org/10.1038/ni.2256
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