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

Liú, Dan; Yan, Jiacong; Sun, Jiahui; Liu, Bo; Ma, Wenxue; Li, Ye; Shao, Xingxing; Qi, Hai

doi:10.1016/j.immuni.2021.08.003

Cited by 41 publications

(24 citation statements)

References 60 publications

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“…Due to space restrictions, we only showed the visualized results of BCL6 and FOXP3. BCL6 is the master transcriptional regulator of Tfh cell differentiation, which is required for germinal center formation and antibody affinity maturation ( 51 ). As gene expression differential analysis showed, compared to the healthy controls, both the untreated TAK group ( p =0.007) and the treated TAK group ( p =0.006) had an increased mRNA level of BCL6 ( Figure 7A ).…”

Section: Resultsmentioning

confidence: 99%

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis

Tian

Huang

et al. 2022

Front. Immunol.

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To explore the relationships between Toll-like receptors (TLRs) and the activation and differentiation of T-cells in Takayasu’s arteritis (TAK), using real-time fluorescence quantitative polymerase chain reaction, mRNA abundance of 29 target genes in peripheral blood mononuclear cells (PBMCs) were detected from 27 TAK patients and 10 healthy controls. Compared with the healthy control group, the untreated TAK group and the treated TAK group had an increased mRNA level of TLR2 and TLR4. A sample-to-sample matrix revealed that 80% of healthy controls could be separated from the TAK patients. Correlation analysis showed that the inactive-treated TAK group exhibited a unique pattern of inverse correlations between the TLRs gene clusters (including TLR1/2/4/6/8, BCL6, TIGIT, NR4A1, etc) and the gene cluster associated with T-cell activation and differentiation (including TCR, CD28, T-bet, GATA3, FOXP3, CCL5, etc). The dynamic gene co-expression network indicated the TAK groups had more active communication between TLRs and T-cell activation than healthy controls. BCL6, CCL5, FOXP3, GATA3, CD28, T-bet, TIGIT, IκBα, and NR4A1 were likely to have a close functional relation with TLRs at the inactive stage. The co-expression of TLR4 and TLR6 could serve as a biomarker of disease activity in treated TAK (the area under curve/sensitivity/specificity, 0.919/100%/90.9%). The largest gene co-expression cluster of the inactive-treated TAK group was associated with TLR signaling pathways, while the largest gene co-expression cluster of the active-treated TAK group was associated with the activation and differentiation of T-cells. The miRNA sequencing of the plasma exosomes combining miRDB, DIANA-TarBase, and miRTarBase databases suggested that the miR-548 family miR-584, miR-3613, and miR-335 might play an important role in the cross-talk between TLRs and T-cells at the inactive stage. This study found a novel relation between TLRs and T-cell in the pathogenesis of autoimmune diseases, proposed a new concept of TLR-co-expression signature which might distinguish different disease activity of TAK, and highlighted the miRNA of exosomes in TLR signaling pathway in TAK.

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Section: Resultsmentioning

confidence: 99%

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis

Tian

Huang

et al. 2022

Front. Immunol.

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“…The molecular rules of cellular exit from the GC reaction are less well understood ( 2, 48, 49 ). Quantitative differences in T FH -GC B cell contact duration and quality play a role ( 6, 50 ). B cell transcriptional changes occur to down-regulate Bcl6 and permit alternate programs and outcomes.…”

Section: Discussionmentioning

confidence: 99%

Follicular helper T cells expressing Blimp1 are specialized for plasma cell differentiation

Miller

Suparski

Higgins

et al. 2022

Preprint

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B cells differentiate into antibody-producing plasma cells (PC) and germinal center (GC) B cells under the guidance of specialized CD4+ follicular helper T (TFH) cells. Here, we demonstrate that CD4 T cells require Prdm1 expression for both early PC differentiation and post-GC PC formation. Using dual Blimp1/Foxp3 reporter mice and single cell-indexed analysis, we segregate persistent compartments and expressed transcriptional programs of Blimp1+ CXCR5+PD1hi TFH (referred to here as PC-TFH) from canonical Blimp1- Bcl6+ TFH (GC-TFH) and Blimp1+Foxp3+ TFR immune regulators. Antigen recall expands localized PC-TFH compartments with rapidly divergent antigenspecific memory PC-TFH and GC-TFH programs. Thus, Blimp1 is a central mediator of PC-TFH function producing specialized TFH subsets that co-ordinate with GC-TFH function to establish highaffinity long-lasting protective immunity to vaccines and infection.

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“…The nuances of DC modulation of Tfh differentiation have been extensively reviewed ( 23 , 24 ). Induction of Bcl6 signaling results in expression CXCR5 on the cell surface, regulates Tfh intracellular calcium signaling, and modulates expression of CD40L ( 9 , 10 , 25 ). While the deletion of one copy of the Bcl6 gene did not significantly alter activation of Tfh or localization of Tfh to follicles, GC formation and maintenance was inhibited.…”

Section: Differentiation Of Tfhmentioning

confidence: 99%

“…While the deletion of one copy of the Bcl6 gene did not significantly alter activation of Tfh or localization of Tfh to follicles, GC formation and maintenance was inhibited. Moreover, overexpression of CD40L could partially rescue GC formation and Tfh maintenance after deletion of the single copy of the Bcl6 gene ( 25 ). This highlights the importance of Bcl6 for Tfh maintenance and signifies that there may be overlapping mechanisms of Bcl6 and CD40L in mediating T:B cell interactions.…”

Section: Differentiation Of Tfhmentioning

confidence: 99%

Providing a Helping Hand: Metabolic Regulation of T Follicular Helper Cells and Their Association With Disease

et al. 2022

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T follicular helper (Tfh) cells provide support to B cells upon arrival in the germinal center, and thus are critical for the generation of a robust adaptive immune response. Tfh express specific transcription factors and cellular receptors including Bcl6, CXCR5, PD-1, and ICOS, which are critical for homing and overall function. Generally, the induction of an immune response is tightly regulated. However, deviation during this process can result in harmful autoimmunity or the inability to successfully clear pathogens. Recently, it has been shown that Tfh differentiation, activation, and proliferation may be linked with the cellular metabolic state. In this review we will highlight recent discoveries in Tfh differentiation and explore how these cells contribute to functional immunity in disease, including autoimmune-related disorders, cancer, and of particular emphasis, during infection.

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

Cited by 41 publications

References 60 publications

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis

Identification of the Association Between Toll-Like Receptors and T-Cell Activation in Takayasu’s Arteritis

Follicular helper T cells expressing Blimp1 are specialized for plasma cell differentiation

Providing a Helping Hand: Metabolic Regulation of T Follicular Helper Cells and Their Association With Disease

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