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Open AccessJournal ArticleDOI

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

TLDR
It is found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo TFH differentiation and T cell help to B cells in mice, and that Bcl 6 and Blimp-1 play central but opposing roles inTFH differentiation.
Abstract
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 (TFH), provides this help; however, the molecular requirements for TFH differentiation are unknown. We found that expression of the transcription factor Bcl6 in CD4+ T cells is both necessary and sufficient for in vivo TFH differentiation and T cell help to B cells in mice. In contrast, the transcription factor Blimp-1, an antagonist of Bcl6, inhibits TFH differentiation and help, thereby preventing B cell germinal center and antibody responses. These findings demonstrate that TFH cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in TFH differentiation.

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Journal ArticleDOI

Differentiation of Effector CD4 T Cell Populations

TL;DR: This review summarizes the discovery, functions, and relationships among Th cells; the cytokine and signaling requirements for their development; the networks of transcription factors involved in their differentiation; the epigenetic regulation of their key cytokines and transcription factors; and human diseases involving defective CD4 T cell differentiation.
Journal ArticleDOI

The regulation of IL-10 production by immune cells

TL;DR: Understanding the specific molecular events that regulate the production of IL-10 will help to answer the remaining questions that are important for the design of new strategies of immune intervention.
Journal ArticleDOI

Follicular Helper CD4 T Cells (TFH)

TL;DR: This review discusses recent progress and areas of uncertainty or disagreement in the literature, and debates the developmental relationship between T(FH) cells and other CD4 T cell subsets (Th1, Th2, Th17, iTreg).
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mRNA vaccines — a new era in vaccinology

TL;DR: A detailed overview of mRNA vaccines is provided and future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use are considered.
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Physiological and pathological roles for microRNAs in the immune system

TL;DR: Recent advances in understanding of both the intended functions of miRNAs in managing immune cell biology and their pathological roles when their expression is dysregulated are discussed.
References
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Journal ArticleDOI

CD4 T cells: fates, functions, and faults

TL;DR: Much of what is known about the 4 CD4 T-cell subsets is summarized, including the history of their discovery, their unique cytokine products and related functions, their distinctive expression of cell surface receptors and their characteristic transcription factors, the regulation of their fate determination, and the consequences of their abnormal activation.
Journal ArticleDOI

A chemokine-driven positive feedback loop organizes lymphoid follicles

TL;DR: It is established that B-lymphocyte chemoattractant (BLC/BCA1) and its receptor, CXCR5, are needed for B-cell homing to follicles in lymph nodes as well as in spleen, and that BLC is required for the development of most lymph nodes and Peyer's patches.
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Generation of T Follicular Helper Cells Is Mediated by Interleukin-21 but Independent of T Helper 1, 2, or 17 Cell Lineages

TL;DR: It is shown that Tfh cells had a distinct gene expression profile and developed in vivo independently of the Th1 or Th2 cell lineages and was dependent on interleukin-21 (IL-21), IL-6, and signal transducer and activator of transcription 3 (STAT3) in vivo.
Journal ArticleDOI

Blimp-1 Orchestrates Plasma Cell Differentiation by Extinguishing the Mature B Cell Gene Expression Program

TL;DR: These findings suggest that Blimp-1 promotes plasmacytic differentiation by extinguishing gene expression important for B cell receptor signaling, germinal center B cell function, and proliferation while allowing expression of important plasma cell genes such as XBP-1.
Journal ArticleDOI

Control of Inflammation, Cytokine Expression, and Germinal Center Formation by BCL-6

TL;DR: Dysregulation of STAT-responsive genes may underlie the inflammatory disease in BCL-6-deficient mice and participate in lymphoid malignancies.
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