Long-lived antigen-induced IgM plasma cells demonstrate somatic mutations and contribute to long-term protection

Caitlin Bohannon, Ryan Powers, Lakshmipriyadarshini Satyabhama, Ang Cui, Christopher Tipton, Miri Michaeli, Ioanna Skountzou, Robert S. Mittler, Steven H. Kleinstein, Ramit Mehr, Frances Eun-Yun Lee, Ignacio Sanz and Joshy Jacob ()
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Caitlin Bohannon: Emory Vaccine Center, Yerkes National Primate Center, Emory University
Ryan Powers: Emory Vaccine Center, Yerkes National Primate Center, Emory University
Lakshmipriyadarshini Satyabhama: Emory Vaccine Center, Yerkes National Primate Center, Emory University
Ang Cui: Yale University
Christopher Tipton: Emory University
Miri Michaeli: Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University
Ioanna Skountzou: Emory Vaccine Center, Yerkes National Primate Center, Emory University
Robert S. Mittler: Emory Vaccine Center, Yerkes National Primate Center, Emory University
Steven H. Kleinstein: Yale University
Ramit Mehr: Computational Immunology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University
Frances Eun-Yun Lee: Emory University
Ignacio Sanz: Emory University
Joshy Jacob: Emory Vaccine Center, Yerkes National Primate Center, Emory University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract Long-lived plasma cells are critical to humoral immunity as a lifelong source of protective antibodies. Antigen-activated B cells—with T-cell help—undergo affinity maturation within germinal centres and persist as long-lived IgG plasma cells in the bone marrow. Here we show that antigen-specific, induced IgM plasma cells also persist for a lifetime. Unlike long-lived IgG plasma cells, which develop in germinal centres and then home to the bone marrow, IgM plasma cells are primarily retained within the spleen and can develop even in the absence of germinal centres. Interestingly, their expressed IgV loci exhibit somatic mutations introduced by the activation-induced cytidine deaminase (AID). However, these IgM plasma cells are probably not antigen-selected, as replacement mutations are spread through the variable segment and not enriched within the CDRs. Finally, antibodies from long-lived IgM plasma cells provide protective host immunity against a lethal virus challenge.

Date: 2016
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DOI: 10.1038/ncomms11826

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