title: The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression.
abstract: Plasma cells (PCs) are the final B-cell differentiation stage. Recent evidence reveals relevant functional differences within the PC compartment. In rodents, early PCs formed in secondary lymphoid tissues show enhanced apoptosis and short life span, whereas PCs present in a final destination organ, such as the bone marrow (BM), have reached a stable prolonged survival state. BM PCs arrive at this organ as a circulating precursor whose cellular nature remains uncertain. An initial aim of this study was to characterize this circulating cell. We hypothesized that antibody-secreting cells detectable in the human blood after immunization might be a candidate precursor. These cells were obtained from the blood of volunteers immunized 6 days earlier with tetanus toxoid (tet), and they were unambiguously identified as PCs, as demonstrated by their expression of the CD38(h) phenotype, by morphology, by immunoglobulin (Ig) intracytoplasmic staining, and by IgG-tet-secreting capacity in vitro. In addition, by using the common CD38(h) feature, human PCs from tonsil (as a possible source of early PCs), from blood from tet-immunized donors (as the putative precursors of BM PCs), and from BM (as a deposit organ) have been purified and their phenotypes compared. The results show that a variety of differentiation molecules, proteins involved in the control of apoptosis, the B-cell transcription factors, positive regulatory domain I-binding factor 1/B lymphocyte-induced maturation protein 1 and B cell-specific activating protein and, at least partially, the chemokine receptor CXCR4 were expressed by human PCs following a gradient of increasing maturity in the direction: tonsil-->blood-->BM. However, PCs from these different organs showed a local pattern of adhesion molecule expression. These observations are discussed in light of the complex physiology of the human PC compartment.
authors.affiliation: Servicio de Inmunología, Hospital Universitario Puerta del Mar, Avenida Ana de Viya 21, 11009 Cádiz, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Medina
authors.forename: Carmen
authors.initials: C
authors.lastname: Segundo
authors.forename: Antonio
authors.initials: A
authors.lastname: Campos-Caro
authors.forename: Inés
authors.initials: I
authors.lastname: González-García
authors.forename: José A
authors.initials: JA
authors.lastname: Brieva
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000032:analysis; D001773:Blood Cells / Q000166:cytology* / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002454:Cell Differentiation; D002465:Cell Movement; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008562:Membrane Glycoproteins; D009244:NAD+ Nucleosidase / Q000032:analysis; D051757:PAX5 Transcription Factor; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000032:analysis; D019707:Receptors, Chemokine / Q000378:metabolism; D012097:Repressor Proteins; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D012097:Repressor Proteins; D013745:Tetanus Toxoid; D014157:Transcription Factors; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1