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.
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14 May 2007
Article|
May 07 2007
Lymphomas can develop from B cells chronically helped by idiotype-specific T cells
Michael M. Zangani,
Michael M. Zangani
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Marianne Frøyland,
Marianne Frøyland
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Gao Yue Qiu,
Gao Yue Qiu
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Leonardo A. Meza-Zepeda,
Leonardo A. Meza-Zepeda
2Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Jeffery L. Kutok,
Jeffery L. Kutok
3Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115
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Keith M. Thompson,
Keith M. Thompson
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Ludvig A. Munthe,
Ludvig A. Munthe
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Bjarne Bogen
Bjarne Bogen
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
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Michael M. Zangani
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
Marianne Frøyland
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
Gao Yue Qiu
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
Leonardo A. Meza-Zepeda
2Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
Jeffery L. Kutok
3Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115
Keith M. Thompson
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
Ludvig A. Munthe
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
Bjarne Bogen
1Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
CORRESPONDENCE Ludvig A. Munthe: [email protected] OR Bjarne Bogen: [email protected]
Abbreviations used: BCR, B cell receptor; CGH, comparative genomic hybridization; H, heavy; IRF-4, interferon regulatory factor 4; VH, variable heavy chain.
L.A. Munthe and B. Bogen contributed equally to this paper.
G.Y. Qiu's present address is Shanghai Shuguang Hospital, 200032 Shanghai, China.
Received:
June 08 2006
Accepted:
April 13 2007
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2007
J Exp Med (2007) 204 (5): 1181–1191.
Article history
Received:
June 08 2006
Accepted:
April 13 2007
Citation
Michael M. Zangani, Marianne Frøyland, Gao Yue Qiu, Leonardo A. Meza-Zepeda, Jeffery L. Kutok, Keith M. Thompson, Ludvig A. Munthe, Bjarne Bogen; Lymphomas can develop from B cells chronically helped by idiotype-specific T cells . J Exp Med 14 May 2007; 204 (5): 1181–1191. doi: https://doi.org/10.1084/jem.20061220
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