BCL6 controls contact-dependent help delivery during follicular T-B cell interactions

BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not apprec...

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Veröffentlicht in:Immunity (Cambridge, Mass.) Mass.), 2021-10, Vol.54 (10), p.2245-2255.e4
Hauptverfasser: Liu, Dan, Yan, Jiacong, Sun, Jiahui, Liu, Bo, Ma, Weiwei, Li, Ye, Shao, Xingxing, Qi, Hai
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container_end_page 2255.e4
container_issue 10
container_start_page 2245
container_title Immunity (Cambridge, Mass.)
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creator Liu, Dan
Yan, Jiacong
Sun, Jiahui
Liu, Bo
Ma, Weiwei
Li, Ye
Shao, Xingxing
Qi, Hai
description BCL6 is required for development of follicular T helper (Tfh) cells to support germinal center (GC) formation. However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not appreciably alter early T cell activation and follicular localization but inhibited GC formation and Tfh cell maintenance. BCL6 impinged on Tfh calcium signaling and also controlled Tfh entanglement with and CD40L delivery to B cells. Amounts of BCL6 protein and nominal frequencies of Tfh cells markedly changed within hours after strengths of T-B cell interactions were altered in vivo, while CD40L overexpression rectified both defective GC formation and Tfh cell maintenance because of the BCL6 haploinsufficiency. Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner. •Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression BCL6 is required for Tfh cell development. Liu et al. show that BCL6 controls calcium signaling of Tfh cells, follicular T-B cell entanglement, and efficient T cell-to-B cell CD40L delivery and promotes Tfh cell maintenance partly in a T cell non-autonomous manner.
doi_str_mv 10.1016/j.immuni.2021.08.003
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However, it is not clear what unique functions programmed by BCL6 can explain its absolute essentiality in T cells for GC formation. We found that ablation of one Bcl6 allele did not appreciably alter early T cell activation and follicular localization but inhibited GC formation and Tfh cell maintenance. BCL6 impinged on Tfh calcium signaling and also controlled Tfh entanglement with and CD40L delivery to B cells. Amounts of BCL6 protein and nominal frequencies of Tfh cells markedly changed within hours after strengths of T-B cell interactions were altered in vivo, while CD40L overexpression rectified both defective GC formation and Tfh cell maintenance because of the BCL6 haploinsufficiency. Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner. •Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression BCL6 is required for Tfh cell development. 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Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner. •Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression BCL6 is required for Tfh cell development. 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Our results reveal BCL6 functions in Tfh cells that are essential for GC formation and suggest that BCL6 helps maintain Tfh cell phenotypes in a T cell non-autonomous manner. •Both copies of Bcl6 gene are required for efficient follicular T-B cell entanglement•BCL6 is required for calcium signaling in Tfh cells and CD40L delivery to B cells•Expression of Tfh markers responds to acute perturbation of T-B cell interactions•Defective functions of BCL6-insufficient T cells are rescued by CD40L overexpression BCL6 is required for Tfh cell development. 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source Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
subjects BCL6
calcium signaling
CD40L
follicle
germinal center
intravital imaging
lymph node
stim1
T-B interactions
Tfh cells
title BCL6 controls contact-dependent help delivery during follicular T-B cell interactions
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