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

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Published online 7 May 2007

doi:10.1084/jem.20061220

The Journal of Experimental Medicine

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

cells

M. Zangani1, nne Frøyland1, Gao Yue Qiu1, Leonardo A. Meza-Zepeda2,

Jeffery L. Kutok3, M. 1, 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@... OR Bjarne Bogen:

b.bogen@...

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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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.