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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}liai.org

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