| Literature DB >> 31422869 |
Melanie S Vacchio1, Thomas Ciucci1, Yayi Gao1, Masashi Watanabe2, Mariah Balmaceno-Criss1, Mitchell T McGinty1, Allan Huang1, Qi Xiao1, Cameron McConkey1, Yongmei Zhao3, Jyoti Shetty3, Bao Tran3, Marion Pepper4, Golnaz Vahedi5, Marc K Jenkins6, Dorian B McGavern7, Rémy Bosselut8.
Abstract
The generation of high-affinity neutralizing antibodies, the objective of most vaccine strategies, occurs in B cells within germinal centers (GCs) and requires rate-limiting "help" from follicular helper CD4+ T (Tfh) cells. Although Tfh differentiation is an attribute of MHC II-restricted CD4+ T cells, the transcription factors driving Tfh differentiation, notably Bcl6, are not restricted to CD4+ T cells. Here, we identified a requirement for the CD4+-specific transcription factor Thpok during Tfh cell differentiation, GC formation, and antibody maturation. Thpok promoted Bcl6 expression and bound to a Thpok-responsive region in the first intron of Bcl6. Thpok also promoted the expression of Bcl6-independent genes, including the transcription factor Maf, which cooperated with Bcl6 to mediate the effect of Thpok on Tfh cell differentiation. Our findings identify a transcriptional program that links the CD4+ lineage with Tfh differentiation, a limiting factor for efficient B cell responses, and suggest avenues to optimize vaccine generation. Published by Elsevier Inc.Entities:
Keywords: Bcl6; CD4 T cells; Maf; Thpok; follicular helper T cells; germinal center reaction
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Year: 2019 PMID： 31422869 PMCID： PMC6904114 DOI： 10.1016/j.immuni.2019.06.023
Source DB: PubMed Journal: Immunity ISSN： 1074-7613 Impact factor: 31.745