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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 (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 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 Dorner, T. Search for Related Content PubMed PubMed Citation Articles by Mei, H. E. Articles by Dorner, T. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 28, 2008 Accepted October 7, 2008 Blood-borne human plasma cells in steady-state are derived from mucosal immune responses Henrik E. Mei*, Taketoshi Yoshida, Wondossen Sime, Falk Hiepe, Kathi Thiele, Rudolf A. Manz, Andreas Radbruch, and Thomas Dorner Center for Tumor Medicine, Institute of Transfusion Medicine, Charite University Hospital, Berlin, Germany Deutsches Rheumaforschungszentrum (DRFZ), Berlin, Germany Department of Rheumatology, Charite University Hospital, Berlin, Germany Center for Musculoskeletal Surgery, Charite University Hospital, Berlin, Germany * Corresponding author; email: mei{at}drfz.de. 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 detectable in human blood at low frequency in any unimmunized donor at any time. In this steady-state, 80% of plasmablasts and plasma cells express IgA. Expression of a functional mucosal chemokine receptor (CCR10) and the adhesion molecule 7-integrin suggests that these cells come from mucosal immune reactions and can home back to mucosal tissue. These blood-borne, CCR10+ plasmablasts also express CXCR4 and are attracted by CXCL12. About 40% of plasma cells in human bone marrow produce IgA, are non-migratory and express 7-integrin and CCR10, suggesting a substantial contribution of mucosal plasma cells to the pool of bone marrow resident, long-lived plasma cells. Between days 6-8 after parenteral tetanus/diphtheria vaccination, intracellular IgG+ cells appear in blood, both CD62L+, 7-integrin-, dividing, vaccine-specific, migratory plasmablasts and non-dividing, non-migratory, 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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