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

• Type of Material: Article
• Authors: Caitlin Bohannon, Emory University; Ryan Powers, Emory University; Lakshmipriyadarshini Satyabhama, Emory University; Ang Cui, Yale University; Christopher Tipton, Emory University; Miri Michaeli, Emory University; Ioanna Skountzou, Emory University; Robert S. Mittler, Emory University; Steven H. Kleinstein, Yale University; Ramit Mehr, Emory University; Frances Eun-Hyung Lee, Emory University; Ignacio Sanz, Emory University; Joshy Jacob, Emory University
• Language: English
• Date: 2016-06-07
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: © 2016, The Author(s)
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms11826
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 7
• Start Page: 11826
• End Page: 11826
• Grant/Funding Information: This study was supported by the NIH/NIAD research grant 1R01AI100110-01.

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.