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Science 25 April 1997:
Vol. 276. no. 5312, pp. 589 - 592
DOI: 10.1126/science.276.5312.589
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Reports

Control of Inflammation, Cytokine Expression, and Germinal Center Formation by BCL-6

Alexander L. Dent, Arthur L. Shaffer, Xin Yu, David Allman, Louis M. Staudt *

The gene encoding the BCL-6 transcriptional repressor is frequently translocated and mutated in diffuse large cell lymphoma. Mice with a disrupted BCL-6 gene developed myocarditis and pulmonary vasculitis, had no germinal centers, and had increased expression of T helper cell type 2 cytokines. The BCL-6 DNA recognition motif resembled sites bound by the STAT (signal transducers and activators of transcription) transcription factors, which mediate cytokine signaling. BCL-6 could repress interleukin-4 (IL-4)-induced transcription when bound to a site recognized by the IL-4-responsive transcription factor Stat6. Thus, dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6-deficient mice and participate in lymphoid malignancies.

A. L. Dent, A. L. Shaffer, X. Yu, L. M. Staudt, Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
D. Allman, Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
*   To whom correspondence should be addressed. E-mail: lstaudt{at}alw.nih.gov

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Genomic expression programs and the integration of the CD28 costimulatory signal in T cell activation.
M. Diehn, A. A. Alizadeh, O. J. Rando, C. L. Liu, K. Stankunas, D. Botstein, G. R. Crabtree, and P. O. Brown (2002)
PNAS 99, 11796-11801
   Abstract »    Full Text »    PDF »
Repression of AP-1 Function: A Mechanism for the Regulation of Blimp-1 Expression and B Lymphocyte Differentiation by the B Cell Lymphoma-6 Protooncogene.
F. H. Vasanwala, S. Kusam, L. M. Toney, and A. L. Dent (2002)
J. Immunol. 169, 1922-1929
   Abstract »    Full Text »    PDF »
Alternative Translocation Breakpoint Cluster Region 5' to BCL-6 in B-cell Non-Hodgkin's Lymphoma.
M. P. Butler, S. Iida, D. Capello, D. Rossi, P. H. Rao, P. Nallasivam, D. C. Louie, S. Chaganti, T. Au, R. D. Gascoyne, et al. (2002)
Cancer Res. 62, 4089-4094
   Abstract »    Full Text »    PDF »
A Putative Silencer Element in the IL-5 Gene Recognized by Bcl6.
M. Arima, H. Toyama, H. Ichii, S. Kojima, S. Okada, M. Hatano, G. Cheng, M. Kubo, T. Fukuda, and T. Tokuhisa (2002)
J. Immunol. 169, 829-836
   Abstract »    Full Text »    PDF »
Class II Histone Deacetylases Are Directly Recruited by BCL6 Transcriptional Repressor.
C. Lemercier, M.-P. Brocard, F. Puvion-Dutilleul, H.-Y. Kao, O. Albagli, and S. Khochbin (2002)
J. Biol. Chem. 277, 22045-22052
   Abstract »    Full Text »    PDF »
The Forkhead Transcription Factor AFX Activates Apoptosis by Induction of the BCL-6 Transcriptional Repressor.
T. T.-L. Tang, D. Dowbenko, A. Jackson, L. Toney, D. A. Lewin, A. L. Dent, and L. A. Lasky (2002)
J. Biol. Chem. 277, 14255-14265
   Abstract »    Full Text »    PDF »
Critical Residues within the BTB Domain of PLZF and Bcl-6 Modulate Interaction with Corepressors.
A. Melnick, G. Carlile, K. F. Ahmad, C.-L. Kiang, C. Corcoran, V. Bardwell, G. G. Prive, and J. D. Licht (2002)
Mol. Cell. Biol. 22, 1804-1818
   Abstract »    Full Text »    PDF »
Dissection of B cell differentiation during primary immune responses in mice with altered CD40 signals.
T. Yasui, M. Muraoka, Y. Takaoka-Shichijo, I. Ishida, N. Takegahara, J. Uchida, A. Kumanogoh, S. Suematsu, M. Suzuki, and H. Kikutani (2002)
Int. Immunol. 14, 319-329
   Abstract »    Full Text »    PDF »
Cutting Edge: STAT6 Serves as a Positive and Negative Regulator of Gene Expression in IL-4-Stimulated B Lymphocytes.
A. J. Schroder, P. Pavlidis, A. Arimura, D. Capece, and P. B. Rothman (2002)
J. Immunol. 168, 996-1000
   Abstract »    Full Text »    PDF »
Friend of GATA-1 Represses GATA-3-dependent Activity in CD4+ T Cells.
M. Zhou, W. Ouyang, Q. Gong, S. G. Katz, J. M. White, S. H. Orkin, and K. M. Murphy (2001)
J. Exp. Med. 194, 1461-1471
   Abstract »    Full Text »    PDF »
Project normal: Defining normal variance in mouse gene expression.
C. C. Pritchard, L. Hsu, J. Delrow, and P. S. Nelson (2001)
PNAS 98, 13266-13271
   Abstract »    Full Text »    PDF »
Regulation of interferon-{gamma} gene expression by nuclear factor of activated T cells.
A. Kiani, F. J. Garcia-Cozar, I. Habermann, S. Laforsch, T. Aebischer, G. Ehninger, and A. Rao (2001)
Blood 98, 1480-1488
   Abstract »    Full Text »    PDF »
Arrested Differentiation, the Self-Renewing Memory Lymphocyte, and Vaccination.
D. T. Fearon, P. Manders, and S. D. Wagner (2001)
Science 293, 248-250
   Abstract »    Full Text »


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