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Science 316 (5824): 604-608

Copyright © 2007 by the American Association for the Advancement of Science

Regulation of the Germinal Center Response by MicroRNA-155

To-Ha Thai,1 Dinis Pedro Calado,1 Stefano Casola,2 K. Mark Ansel,1 Changchun Xiao,1 Yingzi Xue,3 Andrew Murphy,3 David Frendewey,3 David Valenzuela,3 Jeffery L. Kutok,4 Marc Schmidt-Supprian,1 Nikolaus Rajewsky,5 George Yancopoulos,3 Anjana Rao,1 Klaus Rajewsky1*

Abstract: MicroRNAs are small RNA species involved in biological control at multiple levels. Using genetic deletion and transgenic approaches, we show that the evolutionarily conserved microRNA-155 (miR-155) has an important role in the mammalian immune system, specifically in regulating T helper cell differentiation and the germinal center reaction to produce an optimal T cell–dependent antibody response. miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo.

1 CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.
2 IFOM–The FIRC Institute for Molecular Oncology, Milano, Via Adamello 16 Milan 20139, Italy.
3 Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
4 Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
5 Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.

* To whom correspondence should be addressed. E-mail: rajewsky{at}

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R. C. Thompson, M. Herscovitch, I. Zhao, T. J. Ford, and T. D. Gilmore (2011)
J. Biol. Chem. 286, 1675-1682
   Abstract »    Full Text »    PDF »
The Interleukin 13 (IL-13) Pathway in Human Macrophages Is Modulated by MicroRNA-155 via Direct Targeting of Interleukin 13 Receptor {alpha}1 (IL13R{alpha}1).
R. T. Martinez-Nunez, F. Louafi, and T. Sanchez-Elsner (2011)
J. Biol. Chem. 286, 1786-1794
   Abstract »    Full Text »    PDF »
The Art of MicroRNA Research.
E. van Rooij (2011)
Circ. Res. 108, 219-234
   Abstract »    Full Text »    PDF »
Up-regulation of MicroRNA-155 in Macrophages Contributes to Increased Tumor Necrosis Factor {alpha} (TNF{alpha}) Production via Increased mRNA Half-life in Alcoholic Liver Disease.
S. Bala, M. Marcos, K. Kodys, T. Csak, D. Catalano, P. Mandrekar, and G. Szabo (2011)
J. Biol. Chem. 286, 1436-1444
   Abstract »    Full Text »    PDF »
Follicular dendritic cell-dependent drug resistance of non-Hodgkin lymphoma involves cell adhesion-mediated Bim down-regulation through induction of microRNA-181a.
T. Lwin, J. Lin, Y. S. Choi, X. Zhang, L. C. Moscinski, K. L. Wright, E. M. Sotomayor, W. S. Dalton, and J. Tao (2010)
Blood 116, 5228-5236
   Abstract »    Full Text »    PDF »
MicroRNA expression in maturing murine megakaryocytes.
J. B. Opalinska, A. Bersenev, Z. Zhang, A. A. Schmaier, J. Choi, Y. Yao, J. D'Souza, W. Tong, and M. J. Weiss (2010)
Blood 116, e128-e138
   Abstract »    Full Text »    PDF »

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