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Related Concept Videos

B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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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...
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Related Experiment Video

Updated: Nov 1, 2025

Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
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Small Molecule Inhibitors of Activation-Induced Deaminase Decrease Class Switch Recombination in B Cells.

Juan Alvarez-Gonzalez1, Adam Yasgar2, Robert W Maul1

  • 1Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, United States.

ACS Pharmacology & Translational Science
|June 21, 2021
PubMed
Summary
This summary is machine-generated.

Researchers screened over 90,000 compounds to find inhibitors of activation-induced deaminase (AID). Three promising compounds were identified that can mitigate AID activity, offering potential control over base editing technologies.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • Activation-induced deaminase (AID) is crucial for antibody diversity but also implicated in B cell lymphomas.
  • Understanding and controlling AID activity is essential for both basic research and therapeutic applications.

Purpose of the Study:

  • To identify small molecules that can inhibit the enzymatic activity of AID.
  • To explore potential therapeutic strategies for mitigating AID-driven mutagenesis and lymphomagenesis.

Main Methods:

  • Conducted a high-throughput screening of over 90,000 compounds.
  • Assessed AID enzymatic activity using biochemical assays for cytosine deamination.
  • Evaluated AID function in cellular assays measuring class switch recombination in B cells.

Main Results:

  • Identified three compounds that inhibit AID activity in both transformed B cell lines and primary murine splenic B cells.
  • Observed that these inhibitors share similar chemical structures, suggesting a common mechanism of action.
  • Demonstrated that the identified inhibitors specifically block AID without affecting the related cytosine DNA deaminase, APOBEC3B.
  • Determined that AID expression is sustained for several days post-B cell activation.

Conclusions:

  • This study reports the first small molecules capable of inhibiting AID.
  • These inhibitors offer a potential tool for gaining regulatory control over AID activity and base editing.
  • The findings pave the way for developing novel strategies to manage AID-related diseases and advance gene editing technologies.