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Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
Epigenetic Regulation01:46

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Autoimmune Disorders01:29

Autoimmune Disorders

Autoimmune diseases are a group of disorders in which the body's immune system mistakenly attacks its own cells, tissues, and organs. This results from an overactive immune response against substances and tissues normally present in the body. Let's delve into the concept and mechanism of autoimmune diseases from an immune system point of view, explore different causes and examples of such diseases, and discuss potential solutions.
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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation

Published on: September 20, 2017

DNA methylation and B-cell autoreactivity.

Soizic Garaud1, Pierre Youinou, Yves Renaudineau

  • 1Immiunologie and Pathology, Universitéde Brest, Université Européenne de Bretagne, Brest, France.

Advances in Experimental Medicine and Biology
|June 2, 2011
PubMed
Summary
This summary is machine-generated.

DNA methylation regulates B-cell development and autoimmunity. Impaired DNA methylation in autoreactive B cells, especially in systemic lupus erythematosus (SLE), promotes disease. Understanding this mechanism could lead to new therapies.

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Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • DNA methylation at CpG dinucleotides is crucial for B-cell development and the elimination of autoreactive B cells.
  • Expression of B-cell specific factors like Pax5, B-cell receptor (BCR) rearrangement, and cytokine production are regulated by DNA methylation.
  • Autoreactive CD5+ B cells exhibit reduced DNA methylation capacity, leading to the aberrant expression of repressed genes, including human endogenous retroviruses (HERVs).

Purpose of the Study:

  • To investigate the role of DNA methylation in the development and function of B cells, particularly autoreactive B cells.
  • To understand the implications of impaired DNA methylation in autoimmune diseases like systemic lupus erythematosus (SLE).
  • To explore the potential of targeting DNA methylation for therapeutic interventions against autoreactive B cells.

Main Methods:

  • Analysis of DNA methylation patterns in different B-cell populations.
  • Assessment of gene expression in B cells with varying methylation statuses.
  • Evaluation of the effects of demethylating drugs on B-cell autoreactivity.

Main Results:

  • Autoreactive B cells, especially in SLE patients, show an inability to induce DNA methylation, prolonging their survival.
  • Reduced DNA methylation in CD5+ B cells leads to the expression of normally silenced genes (e.g., HERVs).
  • Treatment of B cells with demethylating agents enhances their autoreactivity.

Conclusions:

  • DNA methylation is a critical regulator of B-cell tolerance and immune homeostasis.
  • Defective DNA methylation in B cells contributes to the pathogenesis of autoimmune diseases like SLE.
  • Targeting DNA methylation pathways in B cells presents a promising therapeutic strategy for controlling autoimmunity.