title: Lymphomas can develop from B cells chronically helped by idiotype-specific T cells.
abstract: B cell lymphomas have been associated with chronic infections and autoimmunity. However, most lymphomas develop in the absence of any known chronic antigenic stimulation. B cells process their highly diversified endogenous immunoglobulin and present clonally unique variable-region idiotypic (Id) peptides on their major histocompatibility complex (MHC) class II molecules to Id-specific T cells. We show that B cells chronically helped by Id-specific Th2 cells developed into large B cell lymphomas with cytogenetic DNA aberrations. The lymphomas expressed high amounts of Id, MHC class II, CD80/86, and CD40 and bidirectionally collaborated with Th2 cells. Thus, MHC class II-presented Id peptides may represent a chronic self-antigenic stimulus for T cell-dependent lymphomagenesis. Eventually, B lymphomas grew independent of T cells. Thus, T cells do not only eliminate cancers as currently believed. In fact, Id-specific Th2 cells can induce B lymphomas.
authors.affiliation: Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Zangani
authors.forename: Marianne
authors.initials: M
authors.lastname: Frøyland
authors.forename: Gao Yue
authors.initials: GY
authors.lastname: Qiu
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: Meza-Zepeda
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Keith M
authors.initials: KM
authors.lastname: Thompson
authors.forename: Ludvig A
authors.initials: LA
authors.lastname: Munthe
authors.forename: Bjarne
authors.initials: B
authors.lastname: Bogen
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism; D001483:Base Sequence; D019013:CD40 Antigens / Q000378:metabolism; D005434:Flow Cytometry; D050438:Genes, Immunoglobulin Heavy Chain / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000378:metabolism; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology* / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes