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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes / immunology*
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B-Lymphocytes / metabolism
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B7-1 Antigen / metabolism
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B7-2 Antigen / metabolism
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Base Sequence
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CD40 Antigens / metabolism
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Flow Cytometry
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Genes, Immunoglobulin Heavy Chain / genetics
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Histocompatibility Antigens Class II / metabolism
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Immunoglobulin Idiotypes / metabolism
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Immunohistochemistry
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Lymphoma, Large B-Cell, Diffuse / etiology*
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Lymphoma, Large B-Cell, Diffuse / immunology*
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Mice
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Mice, Transgenic
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Molecular Sequence Data
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Sequence Analysis, DNA
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T-Lymphocyte Subsets / immunology*
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Th2 Cells / immunology*
Substances
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B7-1 Antigen
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B7-2 Antigen
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CD40 Antigens
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Histocompatibility Antigens Class II
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Immunoglobulin Idiotypes
Associated data
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GENBANK/DQ416684
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GENBANK/DQ416685
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GENBANK/DQ416686
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GENBANK/DQ416687
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GENBANK/DQ416688
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GENBANK/DQ416689
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GENBANK/DQ416690
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GENBANK/DQ416691
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GENBANK/DQ416692
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GENBANK/DQ416693
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GENBANK/DQ416694
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GENBANK/DQ416695
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GENBANK/DQ416696
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GENBANK/DQ416697
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GENBANK/DQ416698
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GENBANK/DQ416699
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GENBANK/DQ416700
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GENBANK/DQ416701
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GENBANK/DQ416702
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GENBANK/DQ416703
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GENBANK/DQ416704
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GENBANK/DQ416705
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GENBANK/DQ416706
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GENBANK/DQ416707
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GENBANK/DQ416708
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GENBANK/DQ416709
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GENBANK/DQ416710
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GENBANK/DQ416711
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GENBANK/DQ416712
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GENBANK/DQ416713
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GENBANK/DQ416714
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GENBANK/DQ416715
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GENBANK/DQ416716