title: Blood-borne human plasma cells in steady state are derived from mucosal immune responses.
abstract: 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 beta(7) 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 beta(7) 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(+), beta(7) 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.
authors.affiliation: Center for Tumor Medicine, Institute of Transfusion Medicine, Charité University Hospital, Berlin, Germany. mei@drfz.de
authors.forename: Henrik E
authors.initials: HE
authors.lastname: Mei
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Wondossen
authors.initials: W
authors.lastname: Sime
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Kathi
authors.initials: K
authors.lastname: Thiele
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D022422:Diphtheria-Tetanus Vaccine / Q000494:pharmacology; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects / Q000502:physiology*; D007070:Immunoglobulin A / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D010950:Plasma Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D054447:Receptors, CCR10 / Q000378:metabolism; D014611:Vaccination; D055815:Young Adult
chemical_list: C515706:CCR10 protein, human; D022422:Diphtheria-Tetanus Vaccine; D007070:Immunoglobulin A; D039641:Integrin beta Chains; D054447:Receptors, CCR10; C091368:integrin beta7