The Journal of Experimental Medicine
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Published online May 7, 2007
doi:10.1084/jem.20061220
The Journal of Experimental Medicine, Vol. 204, No. 5, 1181-1191
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Zangani et al.
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ARTICLE

 Lymphomas can develop from B cells chronically helped by idiotype-specific T cells

Michael M. Zangani1, Marianne Frøyland1, Gao Yue Qiu1, Leonardo A. Meza-Zepeda2, Jeffery L. Kutok3, Keith M. Thompson1, Ludvig A. Munthe1, and Bjarne Bogen1

1 Institute of Immunology, University of Oslo and Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
2 Department of Tumor Biology, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway
3 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115

CORRESPONDENCE Ludvig A. Munthe: l.a.munthe{at}medisin.uio.no OR Bjarne Bogen: b.bogen{at}medisin.uio.no

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.

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.


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