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

B. Hilda 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

Research output: Contribution to journalArticle

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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 1997
Externally publishedYes

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Germinal Center
Proto-Oncogenes
B-Lymphocytes
Inflammation
T-Lymphocytes
Zinc Fingers
Eosinophils
Genetic Promoter Regions
Non-Hodgkin's Lymphoma
Immunoglobulin E
Antibody Formation
Lymphoma
Cell Proliferation
Genes
Neoplasms

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Ye, B. H., Cattoretti, G., Shen, Q., Zhang, J., Hawe, N., De Waard, R., ... 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

The BCL-6 proto-oncogene controls germinal-centre formation and Th2- type inflammation. / Ye, B. Hilda; Cattoretti, Giorgio; Shen, Qiong; Zhang, Jiandong; Hawe, Nicola; De Waard, Rick; Leung, Cynthia; Nouri-Shirazi, Mahyar; Orazi, Attilio; Chaganti, R. S K; Rothman, Paul; Stall, Alan M.; Pandolfi, Pier Paolo; Dalla-Favera, Riccardo.

In: Nature Genetics, Vol. 16, No. 2, 06.1997, p. 161-170.

Research output: Contribution to journalArticle

Ye, BH, Cattoretti, G, Shen, Q, Zhang, J, Hawe, N, De Waard, R, Leung, C, Nouri-Shirazi, M, Orazi, A, Chaganti, RSK, Rothman, P, Stall, AM, Pandolfi, PP & Dalla-Favera, R 1997, 'The BCL-6 proto-oncogene controls germinal-centre formation and Th2- type inflammation', Nature Genetics, vol. 16, no. 2, pp. 161-170. https://doi.org/10.1038/ng0697-161
Ye, B. Hilda ; Cattoretti, Giorgio ; Shen, Qiong ; Zhang, Jiandong ; Hawe, Nicola ; De Waard, Rick ; Leung, Cynthia ; Nouri-Shirazi, Mahyar ; Orazi, Attilio ; Chaganti, R. S K ; Rothman, Paul ; Stall, Alan M. ; Pandolfi, Pier Paolo ; Dalla-Favera, Riccardo. / The BCL-6 proto-oncogene controls germinal-centre formation and Th2- type inflammation. In: Nature Genetics. 1997 ; Vol. 16, No. 2. pp. 161-170.
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