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

Science  21 Aug 2009:
Vol. 325, Issue 5943, pp. 1006-1010
DOI: 10.1126/science.1175870

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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.

  • * These authors contributed equally to this work.

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