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 C. Leung,Mahyar Nouri-Shirazi,Attilio Orazi,R. S. K. Chaganti,Paul B. Rothman,Alan M. Stall,Pier Paolo Pandolfi,Riccardo Dalla-Favera +13 more
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TLDR
BCL-6 functions as a transcriptional switch that controls germinal centre formation and may also modulate specific T-cell-mediated responses and develop an inflammatory response in multiple organs typical of a Th2-mediated hyperimmune response.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.read more
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Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
Ash A. Alizadeh,Michael B. Eisen,R. Eric Davis,Izidore S. Lossos,Andreas Rosenwald,Jennifer C. Boldrick,Hajeer Sabet,Truc Tran,Xin Yu,John Powell,Liming Yang,Gerald E. Marti,Troy Moore,James I. Hudson,Li-Sheng Lu,David B. Lewis,Robert Tibshirani,Gavin Sherlock,Wing C. Chan,Timothy C. Greiner,Dennis D. Weisenburger,James O. Armitage,Roger A. Warnke,Ronald Levy,Wyndham H. Wilson,M. R. Grever,John C. Byrd,David Botstein,Patrick O. Brown,Louis M. Staudt +29 more
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Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.
Robert J. Johnston,Amanda C. Poholek,Daniel DiToro,Isharat Yusuf,Danelle Eto,Burton E. Barnett,Alexander L. Dent,Joe Craft,Shane Crotty,Shane Crotty +9 more
TL;DR: It is found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo TFH differentiation and T cell help to B cells in mice, and that Bcl 6 and Blimp-1 play central but opposing roles inTFH differentiation.
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Bcl6 Mediates the Development of T Follicular Helper Cells
Roza Nurieva,Yeonseok Chung,Gustavo J. Martinez,Xuexian O. Yang,Shinya Tanaka,Tatyana D. Matskevitch,Yi Hong Wang,Chen Dong +7 more
TL;DR: It is demonstrated that the transcription factor Bcl6 is both necessary and sufficient for TFH differentiation and subsequent B cell–mediated immunity, suggesting that it is a master regulator of this lineage.
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Signaling through the JAK/STAT pathway, recent advances and future challenges.
TL;DR: Significant progress has been made in the characterization of the JAK/STAT signaling cascade, including the identification of multiple STATs and regulatory proteins, and the solution of the crystal structure of two STATs has and will continue to facilitate the understanding of how STATs function.
Journal ArticleDOI
The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment
Di Yu,Sudha Rao,Louis M. Tsai,Sau K. Lee,Yiqing He,Elissa L Sutcliffe,Mnika Srivastava,Michelle A. Linterman,Lei Zheng,Nicholas Simpson,Julia I. Ellyard,Ian A. Parish,Cindy S. Ma,Qi-Jing Li,Christopher R. Parish,Charles R. Mackay,Charles R. Mackay,Carola G. Vinuesa +17 more
TL;DR: It is shown that Bcl-6 positively directs Tfh cell differentiation, through combined repression of miRNAs and transcription factors.
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