title: T cell-dependent survival of CD20+ and CD20- plasma cells in human secondary lymphoid tissue.
abstract: The signals mediating human plasma cell survival in vivo, particularly within secondary lymphoid tissue, are unclear. Human tonsils grafted into immunodeficient mice were therefore used to delineate the mechanisms promoting the survival of plasma cells. Tonsillar plasma cells were maintained within the grafts and the majority were nonproliferating, indicating a long-lived phenotype. A significant depletion of graft plasma cells was observed after anti-CD20 treatment, consistent with the expression of CD20 by most of the cells. Moreover, anti-CD52 treatment caused the complete loss of all graft lymphocytes, including plasma cells. Unexpectedly, anti-CD3, but not anti-CD154, treatment caused the complete loss of plasma cells, indicating an essential role for T cells, but not CD40-CD154 interactions in plasma cell survival. The in vitro coculture of purified tonsillar plasma cells and T cells revealed a T-cell survival signal requiring cell contact. Furthermore, immunofluorescence studies detected a close association between human plasma cells and T cells in vivo. These data reveal that human tonsil contains long-lived plasma cells, the majority of which express CD20 and can be deleted with anti-CD20 therapy. In addition, an important role for contact-dependent interactions with T cells in human plasma cell survival within secondary lymphoid tissue was identified.
authors.affiliation: B Cell Biology Group, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA
authors.forename: David R
authors.initials: DR
authors.lastname: Withers
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorini
authors.forename: Randy T
authors.initials: RT
authors.lastname: Fischer
authors.forename: Rachel
authors.initials: R
authors.lastname: Ettinger
authors.forename: Peter E
authors.initials: PE
authors.lastname: Lipsky
authors.forename: Amrie C
authors.initials: AC
authors.lastname: Grammer
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018951:Antigens, CD20 / Q000096:biosynthesis*; D000951:Antigens, Neoplasm / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D023201:CD40 Ligand / Q000096:biosynthesis; D000074301:CD52 Antigen; D049109:Cell Proliferation; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D014066:Palatine Tonsil / Q000378:metabolism*; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D018951:Antigens, CD20; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D000074301:CD52 Antigen; C000613862:CD52 protein, human; D006023:Glycoproteins; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand