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Science 325 (5943): 1006-1010

Copyright © 2009 by the American Association for the Advancement of Science

Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation

Robert J. Johnston,1,2,* Amanda C. Poholek,3,* Daniel DiToro,1 Isharat Yusuf,1 Danelle Eto,1 Burton Barnett,1 Alexander L. Dent,4 Joe Craft,5,6 Shane Crotty1,2,{dagger}

Abstract: Effective B cell–mediated immunity and antibody responses often require help from CD4+ T cells. It is thought that a distinct CD4+ effector T cell subset, called T follicular helper cells (TFH), provides this help; however, the molecular requirements for TFH differentiation are unknown. We 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. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits TFH differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that TFH cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in TFH differentiation.

1 Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), 9420 Athena Circle, La Jolla, CA 92037, USA.
2 Department of Medicine, University of California, San Diego School of Medicine, La Jolla, CA 92037, USA.
3 Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
4 Department of Microbiology and Immunology and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
5 Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
6 Section of Rheumatology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: shane{at}

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An extended set of PRDM1/BLIMP1 target genes links binding motif type to dynamic repression.
G. M. Doody, M. A. Care, N. J. Burgoyne, J. R. Bradford, M. Bota, C. Bonifer, D. R. Westhead, and R. M. Tooze (2010)
Nucleic Acids Res. 38, 5336-5350
   Abstract »    Full Text »    PDF »
B and T Lymphocyte Attenuator Suppresses IL-21 Production from Follicular Th Cells and Subsequent Humoral Immune Responses.
D. Kashiwakuma, A. Suto, Y. Hiramatsu, K. Ikeda, H. Takatori, K. Suzuki, S.-i. Kagami, K. Hirose, N. Watanabe, I. Iwamoto, et al. (2010)
J. Immunol. 185, 2730-2736
   Abstract »    Full Text »    PDF »
Regulation of the IL-21 Gene by the NF-{kappa}B Transcription Factor c-Rel.
G. Chen, K. Hardy, K. Bunting, S. Daley, L. Ma, and M. F. Shannon (2010)
J. Immunol. 185, 2350-2359
   Abstract »    Full Text »    PDF »
Proinflammatory T helper type 17 cells are effective B-cell helpers.
M. Mitsdoerffer, Y. Lee, A. Jager, H.-J. Kim, T. Korn, J. K. Kolls, H. Cantor, E. Bettelli, and V. K. Kuchroo (2010)
PNAS 107, 14292-14297
   Abstract »    Full Text »    PDF »
Genome-Wide Identification of Human FOXP3 Target Genes in Natural Regulatory T Cells.
T. J. Sadlon, B. G. Wilkinson, S. Pederson, C. Y. Brown, S. Bresatz, T. Gargett, E. L. Melville, K. Peng, R. J. D'Andrea, G. G. Glonek, et al. (2010)
J. Immunol. 185, 1071-1081
   Abstract »    Full Text »    PDF »
Blimp-1's Maiden Flight.
K. Calame (2010)
J. Immunol. 185, 3-4
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