Immunoglobulin class-switch recombination occurs in mantle cell lymphomas

J Pathol. 2006 Jun;209(2):250-7. doi: 10.1002/path.1961.

Abstract

Mantle cell lymphoma (MCL) is an IgM-expressing B cell lymphoma that originates from naive B cells and responds poorly to chemotherapy. We show here that several MCLs harbour isotype-switched subclones. Similar to the situation in normal B cells, in vitro stimulation of MCL cell lines with CD40 ligand (CD40L) and interleukin-4 induced expression of activation-induced cytidine deaminase (AID) and germline transcription at the immunoglobulin heavy chain gene locus. Additionally, the occurrence of switch-circle transcripts and mature IgG transcripts after stimulation indicated ongoing class-switch recombination in mantle cell lymphoma cell lines. Furthermore, stimulation of primary MCL cells in vitro induced expression of class-switched IgG mRNA in the tumour cells. Our data indicate that mantle cell lymphomas have retained the ability to undergo class-switch recombination if appropriate stimuli, such as the CD40 ligand, are provided.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD40 Antigens / immunology
  • Cell Line, Tumor
  • Cytidine Deaminase / immunology
  • Dendritic Cells, Follicular / immunology
  • Genes, Immunoglobulin Heavy Chain / genetics
  • Genes, Immunoglobulin Heavy Chain / immunology
  • Humans
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin Class Switching / immunology
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunohistochemistry / methods
  • Interleukin-4 / immunology
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / immunology
  • Mutation / genetics
  • Mutation / immunology
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Recombination, Genetic / genetics
  • Recombination, Genetic / immunology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Transcription, Genetic / genetics
  • Transcription, Genetic / immunology

Substances

  • CD40 Antigens
  • Immunoglobulin G
  • RNA, Messenger
  • RNA, Neoplasm
  • Interleukin-4
  • Cytidine Deaminase