Blood-borne human plasma cells in steady state are derived from mucosal immune responses

  • Henrik E. Mei
    Center for Tumor Medicine, Institute of Transfusion Medicine, Charité University Hospital, Berlin;
  • Taketoshi Yoshida
    Deutsches Rheumaforschungszentrum (DRFZ), Berlin; and
  • Wondossen Sime
    Deutsches Rheumaforschungszentrum (DRFZ), Berlin; and
  • Falk Hiepe
    Deutsches Rheumaforschungszentrum (DRFZ), Berlin; and
  • Kathi Thiele
    Center for Musculoskeletal Surgery, Charité University Hospital, Berlin, Germany
  • Rudolf A. Manz
    Deutsches Rheumaforschungszentrum (DRFZ), Berlin; and
  • Andreas Radbruch
    Deutsches Rheumaforschungszentrum (DRFZ), Berlin; and
  • Thomas Dörner
    Center for Tumor Medicine, Institute of Transfusion Medicine, Charité University Hospital, Berlin;

書誌事項

公開日
2009-03-12
DOI
  • 10.1182/blood-2008-04-153544
公開者
American Society of Hematology

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説明

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

収録刊行物

  • Blood

    Blood 113 (11), 2461-2469, 2009-03-12

    American Society of Hematology

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