title: Survival of human circulating antigen-induced plasma cells is supported by plasma cell-niche cytokines and T follicular helper lymphocytes.
abstract: Human circulating Ag-induced plasma cells (PCs) contain a high proportion of cycling cells. This study reveals that these PCs spontaneously proliferate in culture during 72 h, as determined by BrdU-uptake detection. Transcriptome analysis indicates that, in comparison with tonsil and bone marrow (BM) PCs, these PCs distinctively upregulate genes involved in cell division. Blood PC proliferation occurs simultaneously with increasing apoptosis rates, and is associated with PC survival. In addition, the proliferating activity of these PCs is enhanced by the addition of cytokines present in PC survival niches. Moreover, blood Ag-induced, but not BM, PCs exhibit the expression of molecules involved in the interaction between memory B cells and T follicular helper (Tfh) cells. In fact, purified circulating and tonsil Tfh cells increased IgG secretion by blood Ag-induced, but not by BM, PCs. This effect is exerted by augmenting blood PC survival through a mechanism partly dependent on cell contact. These results strongly suggest that the proliferating capacity of circulating Ag-induced PCs contributes to their competitive migration to survival niches, either to long-living PC niches or to temporal niches present in reactive lymphoid organs and inflamed tissues, structures where Tfh cells appear to participate.
authors.affiliation: Unidad de Investigación, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain;
authors.forename: Ana
authors.initials: A
authors.lastname: Ramos-Amaya
authors.affiliation: Unidad de Investigación, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain;
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rodríguez-Bayona
authors.affiliation: Servicio de Inmunología, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain;
authors.forename: Rubén
authors.initials: R
authors.lastname: López-Blanco
authors.affiliation: Unidad de Genómica, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Seville, Spain; and Consejo Superior de Investigaciones Científicas, 28008 Madrid, Spain.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Andújar
authors.affiliation: Unidad de Genómica, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Seville, Spain; and.
authors.forename: Mónica
authors.initials: M
authors.lastname: Pérez-Alegre
authors.affiliation: Unidad de Investigación, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain;
authors.forename: Antonio
authors.initials: A
authors.lastname: Campos-Caro
authors.affiliation: Unidad de Investigación, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain; Servicio de Inmunología, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain; josea.brieva.sspa@juntadeandalucia.es.
authors.forename: José A
authors.initials: JA
authors.lastname: Brieva
mesh_terms: D000941:Antigens / Q000276:immunology; D002450:Cell Communication; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016000:Cluster Analysis; D016207:Cytokines / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000276:immunology / Q000378:metabolism; D010641:Phenotype; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000941:Antigens; D016207:Cytokines