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J Immunol. 2015 Jun 15;194(12):5599-603. doi: 10.4049/jimmunol.1500200. Epub 2015 May 8.

Cutting edge: T follicular helper cell differentiation is defective in the absence of Bcl6 BTB repressor domain function.

Author information

1
Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, La Jolla, CA 92037;
2
Genentech, South San Francisco, CA 94080; and.
3
RIKEN Research Center for Allergy and Immunology, Yokohama City, Kanagawa 230-0045, Japan.
4
Division of Vaccine Discovery, La Jolla Institute of Allergy and Immunology, La Jolla, CA 92037; shane@lji.org.

Abstract

T follicular helper (Tfh) cells are essential for germinal centers (GCs) and most long-term humoral immunity. Differentiation of Tfh cells depends on the transcriptional repressor B cell CLL/lymphoma 6 (Bcl6). Bcl6 mediates gene repression via the recruitment of corepressors. Currently, it is unknown how Bcl6 recruits corepressors to regulate gene expression of Tfh cells. In this article, we demonstrate, using a mutant form of Bcl6 with two BTB (bric-a-brac, tramtrack, broad-complex) mutations that abrogate corepressor binding, that the Bcl6 BTB domain is required for proper differentiation of Tfh and GC-Tfh cells in vivo. Importantly, we also observe a significant defect in GC B cell development. These results are consistent in multiple contexts, including a novel lymphocytic choriomeningitis virus nucleoprotein-specific TCR-transgenic mouse model. Taken together, these data suggest that the Bcl6 BTB domain is a key mediator of the differentiation of Tfh cells.

PMID:
25957170
PMCID:
PMC4456636
DOI:
10.4049/jimmunol.1500200
[Indexed for MEDLINE]
Free PMC Article

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