Lymphomas can develop from B cells chronically helped by idiotype-specific T cells.
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.
Zangani
Michael M
MM
Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway.
Frøyland
Marianne
M
Qiu
Gao Yue
GY
Meza-Zepeda
Leonardo A
LA
Kutok
Jeffery L
JL
Thompson
Keith M
KM
Munthe
Ludvig A
LA
Bogen
Bjarne
B
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*
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D007130:Immunoglobulin Idiotypes