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

Bihui H. Ye, Giorgio Cattoretti, Qiong Shen, Jiandong Zhang, Nicola Hawe, Rick De Waard, Cynthia Leung, Mahyar Nouri-Shirazi, Attilio Orazi, R. S.K. Chaganti, Paul Rothman, Alan M. Stall, Pier Paolo Pandolfi, Riccardo Dalla-Favera

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633 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)161-170
Number of pages10
JournalNature Genetics
Volume16
Issue number2
DOIs
StatePublished - Jun 1 1997
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Ye, B. H., Cattoretti, G., Shen, Q., Zhang, J., Hawe, N., De Waard, R., Leung, C., Nouri-Shirazi, M., Orazi, A., Chaganti, R. S. K., Rothman, P., Stall, A. M., Pandolfi, P. P., & Dalla-Favera, R. (1997). The BCL-6 proto-oncogene controls germinal-centre formation and Th2- type inflammation. Nature Genetics, 16(2), 161-170. https://doi.org/10.1038/ng0697-161