Lymphomas Can Develop From B Cells Chronically Helped by Idiotype-Specific T Cells

J Exp Med. 2007 May 14;204(5):1181-91. doi: 10.1084/jem.20061220. Epub 2007 May 7.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • B7-1 Antigen / metabolism
  • B7-2 Antigen / metabolism
  • Base Sequence
  • CD40 Antigens / metabolism
  • Flow Cytometry
  • Genes, Immunoglobulin Heavy Chain / genetics
  • Histocompatibility Antigens Class II / metabolism
  • Immunoglobulin Idiotypes / metabolism
  • Immunohistochemistry
  • Lymphoma, Large B-Cell, Diffuse / etiology*
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Sequence Analysis, DNA
  • T-Lymphocyte Subsets / immunology*
  • Th2 Cells / immunology*

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD40 Antigens
  • Histocompatibility Antigens Class II
  • Immunoglobulin Idiotypes

Associated data

  • GENBANK/DQ416684
  • GENBANK/DQ416685
  • GENBANK/DQ416686
  • GENBANK/DQ416687
  • GENBANK/DQ416688
  • GENBANK/DQ416689
  • GENBANK/DQ416690
  • GENBANK/DQ416691
  • GENBANK/DQ416692
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  • GENBANK/DQ416694
  • GENBANK/DQ416695
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  • GENBANK/DQ416698
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  • GENBANK/DQ416700
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  • GENBANK/DQ416702
  • GENBANK/DQ416703
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  • GENBANK/DQ416705
  • GENBANK/DQ416706
  • GENBANK/DQ416707
  • GENBANK/DQ416708
  • GENBANK/DQ416709
  • GENBANK/DQ416710
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  • GENBANK/DQ416712
  • GENBANK/DQ416713
  • GENBANK/DQ416714
  • GENBANK/DQ416715
  • GENBANK/DQ416716