The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation

Nat Genet. 1997 Jun;16(2):161-70. doi: 10.1038/ng0697-161.


Structural alterations of the promoter region of the BCL-6 proto-oncogene represent the most frequent genetic alteration associated with non-Hodgkin lymphoma, a malignancy often deriving from germinal-centre B cells. The BCL-6 gene encodes a zinc-finger transcriptional repressor normally expressed in both B cells and CD4+ T cells within germinal centres, but its precise function is unknown. We show that mice deficient in BCL-6 displayed normal B-cell, T-cell and lymphoid-organ development but have a selective defect in T-cell-dependent antibody responses. This defect included a complete lack of affinity maturation and was due to the inability of follicular B cells to proliferate and form germinal centres. In addition, BCL-6-deficient mice developed an inflammatory response in multiple organs characterized by infiltrations of eosinophils and IgE-bearing B lymphocytes typical of a Th2-mediated hyperimmune response. Thus, BCL-6 functions as a transcriptional switch that controls germinal centre formation and may also modulate specific T-cell-mediated responses. Altered expression of BCL-6 in lymphoma represents a deregulation of the pathway normally leading to B cell proliferation and germinal centre formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • Bacterial Infections / genetics
  • Cell Differentiation
  • Cell Division
  • DNA-Binding Proteins / genetics*
  • Germ Cells
  • Inflammation / genetics*
  • Lymphoid Tissue / cytology
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-6
  • Th2 Cells / cytology*
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors