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Regulation of the Germinal Center Response by MicroRNA-155
To-Ha Thai,1Dinis Pedro Calado,1Stefano Casola,2K. Mark Ansel,1Changchun Xiao,1Yingzi Xue,3Andrew Murphy,3David Frendewey,3David Valenzuela,3Jeffery L. Kutok,4Marc Schmidt-Supprian,1Nikolaus Rajewsky,5George Yancopoulos,3Anjana Rao,1Klaus Rajewsky1*
MicroRNAs are small RNA species involved in biological controlat 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, specificallyin regulating T helper cell differentiation and the germinalcenter reaction to produce an optimal T cell–dependentantibody response. miR-155 exerts this control, at least inpart, by regulating cytokine production. These results alsosuggest that individual microRNAs can exert critical controlover 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}cbr.med.harvard.edu
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