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Blood, 12 March 2009, Vol. 113, No. 11, pp. 2461-2469. Prepublished online as a Blood First Edition Paper on November 5, 2008; DOI 10.1182/blood-2008-04-153544. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-04-153544v1 113/11/2461    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mei, H. E. Articles by Dörner, T. Search for Related Content PubMed PubMed Citation Articles by Mei, H. E. Articles by Dörner, T. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Blood-borne human plasma cells in steady state are derived from mucosal immune responses Henrik E. Mei1,2, Taketoshi Yoshida2,3, Wondossen Sime2,3, Falk Hiepe2,3, Kathi Thiele4, Rudolf A. Manz2, Andreas Radbruch*,2, and Thomas Dörner*,1,2 1 Center for Tumor Medicine, Institute of Transfusion Medicine, Charité University Hospital, Berlin; 2 Deutsches Rheumaforschungszentrum (DRFZ), Berlin; and 3 Department of Rheumatology and 4 Center for Musculoskeletal Surgery, Charité University Hospital, Berlin, Germany Providing humoral immunity, antibody-secreting plasma cells and their immediate precursors, the plasmablasts, are generated in systemic and mucosal immune reactions. Despite their key role in maintaining immunity and immunopathology, little is known about their homeostasis. Here we show that plasmablasts and plasma cells are always detectable in human blood at low frequency in any unimmunized donor. In this steady state, 80% of plasmablasts and plasma cells express immunoglobulin A (IgA). Expression of a functional mucosal chemokine receptor, C-C motif receptor 10 (CCR10) and the adhesion molecule β7 integrin suggests that these cells come from mucosal immune reactions and can return to mucosal tissue. These blood-borne, CCR10+ plasmablasts also are attracted by CXCL12. Approximately 40% of plasma cells in human bone marrow are IgA+, nonmigratory, and express β7 integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to bone marrow resident, long-lived plasma cells. Six to 8 days after parenteral tetanus/diphtheria vaccination, intracellular IgG+ cells appear in blood, both CD62L+, β7 integrin–, dividing, vaccine-specific, migratory plasmablasts and nondividing, nonmigratory, CD62L– plasma cells of different specificities. Systemic vaccination does not impact on peripheral IgA+ plasmablast numbers, indicating that mucosal and systemic humoral immune responses are regulated independent of each other. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Yuvaraj, G. Dijkstra, J. G. M. Burgerhof, P. M. Dammers, M. Stoel, A. Visser, F. G. M. Kroese, and N. A. Bos Evidence for Local Expansion of IgA Plasma Cell Precursors in Human Ileum J. Immunol., October 15, 2009; 183(8): 4871 - 4878. [Abstract] [Full Text] [PDF]

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