Periodical
The BCL-6proto-oncogene controls germinal-centre formation and Th2-type inflammation
العنوان: | The BCL-6proto-oncogene controls germinal-centre formation and Th2-type inflammation |
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المؤلفون: | Ye, Bihui H., Cattoretti, Giorgio, Shen, Qiong, Zhang, Jiandong, Hawe, Nicola, Waard, Rick de, Leung, Cynthia, Nouri-Shirazi, Mahyar, Orazi, Attilio, Chaganti, R.S.K., Rothman, Paul, Stall, Alan M., Pandolfi, Pier-Paolo, Dalla-Favera, Riccardo |
المصدر: | Nature Genetics; June 1997, Vol. 16 Issue: 2 p161-170, 10p |
مستخلص: | Structural alterations of the promoter region of the BCL-6proto-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. |
قاعدة البيانات: | Supplemental Index |
تدمد: | 10614036 15461718 |
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DOI: | 10.1038/ng0697-161 |