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

Nature Genetics volume 16, pages 161–170 (1997)Cite this article

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 represser 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.

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Authors and Affiliations

  1. Departments of Pathology, Columbia University, New York, New York, 10032, USA

    Bihui H. Ye, Giorgio Cattoretti, Qiong Shen, Jiandong Zhang & Riccardo Dalla-Favera

  2. Department of Human Genetics,

    Bihui H. Ye, Giorgio Cattoretti, Qiong Shen, Jiandong Zhang & Riccardo Dalla-Favera

  3. Departments of Genetics and Development, Department of Human Genetics, Columbia University, New York, New York, 10032, USA

    Riccardo Dalla-Favera

  4. Departments of Microbiology, Columbia University, New York, New York, 10032, USA

    Rick de Waard, Cynthia Leung, Mahyar Nouri-Shirazi, Paul Rothman & Alan M. Stall

  5. Department of Human Genetics, Molecular Biology, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA

    Nicola Hawe & Pier-Paolo Pandolfi

  6. Department of Cell Biology Programs, Memorial Sloan-Kettering Cancer Center, New York, New York, 10021, USA

    R.S.K. Chaganti

  7. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA

    Attilio Orazi

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Correspondence to Riccardo Dalla-Favera.

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Ye, B., Cattoretti, G., Shen, Q. et al. The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type inflammation. Nat Genet 16, 161–170 (1997). https://doi.org/10.1038/ng0697-161

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