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Science. 2009 Aug 21;325(5943):1006-10. doi: 10.1126/science.1175870. Epub 2009 Jul 16.

Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation.

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  • 1Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology (LIAI), 9420 Athena Circle, La Jolla, CA 92037, USA.


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 (T(FH)), provides this help; however, the molecular requirements for T(FH) differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo T(FH) differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits T(FH) differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation.

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