title: Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response.
abstract: Maintenance of protective humoral immunity depends on the generation and survival of antibody-secreting cells. The bone marrow provides niches for long-term survival of plasma cells generated in the course of systemic immune responses in secondary lymphoid organs. Here, we have analyzed migratory human plasma blasts and plasma cells after secondary vaccination with tetanus toxin. On days 6 and 7 after immunization, CD19(+)/CD27(high)/intracellular immunoglobulin G(high) (IgG(high))/HLA-DR(high)/CD38(high)/CD20(-)/CD95(+) tetanus toxin-specific antibody-secreting plasma blasts were released in large numbers from the secondary lymphoid organs into the blood. These cells show chemotactic responsiveness toward ligands for CXCR3 and CXCR4, probably guiding them to the bone marrow or inflamed tissue. At the same time, a population of CD19(+)/CD27(high)/intracellular IgG(high)/HLA-DR(low)/CD38(+)/CD20(-)/CD95(+) cells appeared in the blood in large numbers. These cells, with the phenotype of long-lived plasma cells, secreted antibodies of unknown specificity, not tetanus toxoid. The appearance of these plasma cells in the blood indicates successful competition for survival niches in the bone marrow between newly generated plasma blasts and resident plasma cells as a fundamental mechanism for the establishment of humoral memory and its plasticity.
authors.affiliation: Department of Medicine, Charité, Humbold University, D-10117 Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Odendahl
authors.forename: Henrik
authors.initials: H
authors.lastname: Mei
authors.forename: Bimba F
authors.initials: BF
authors.lastname: Hoyer
authors.forename: Annett M
authors.initials: AM
authors.lastname: Jacobi
authors.forename: Arne
authors.initials: A
authors.lastname: Hansen
authors.forename: Gwendolin
authors.initials: G
authors.lastname: Muehlinghaus
authors.forename: Claudia
authors.initials: C
authors.lastname: Berek
authors.forename: Falk
authors.initials: F
authors.lastname: Hiepe
authors.forename: Rudi
authors.initials: R
authors.lastname: Manz
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Thomas
authors.initials: T
authors.lastname: Dörner
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology; D018941:Antigens, CD19 / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007700:Kinetics; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D018941:Antigens, CD19; C515255:CXCL12 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054377:Chemokine CXCL12; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D018985:Epitopes, B-Lymphocyte; D006684:HLA-DR Antigens; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D013745:Tetanus Toxoid; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014614:Vaccines, Synthetic