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Related Experiment Video

Updated: Oct 12, 2025

Induction and Assessment of Class Switch Recombination in Purified Murine B Cells
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Loop extrusion promotes an alternate pathway for isotype switching.

Hong Ming Shen1, Robert Wuerffel1, Jose F Cantillo1

  • 1Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL 60612-7344, USA.

Cell Reports
|November 24, 2021
PubMed
Summary

Class-switch recombination (CSR) uses asymmetric loop extrusion to create immunoglobulin E+ B cells, bypassing sequential switching. A novel BCR-negative cell intermediate is key for efficient CSR.

Keywords:
AID targetingB cellsBCR-negative B cellsDNA breaksIgEchromatin loopingimmunoglobulin class switch recombinationloop extrusionsequential switching

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Class-switch recombination (CSR) replaces the Cμ constant region with other downstream CH regions.
  • CSR is initiated by activation-induced cytidine deaminase (AID)-mediated DNA breaks in transcriptionally active switch (S) regions.

Purpose of the Study:

  • To elucidate the mechanism of CSR, focusing on the role of S region promoters (Prs) and enhancers.
  • To identify alternative CSR pathways and their impact on B cell populations.

Main Methods:

  • Analysis of diagnostic CSR products in B cell subsets.
  • Investigating chromatin looping and enhancer interactions during CSR.

Main Results:

  • Asymmetric loop extrusion allows 3'Eα to track the locus, forming Pr-Pr-E interactions for CSR between downstream S regions.
  • A novel pathway bypasses sequential switching, leading to immunoglobulin (Ig)E+ B cells without IgG1 expression.
  • A BCR-negative cell intermediate is identified as crucial for efficient CSR.

Conclusions:

  • Asymmetric loop extrusion represents an alternative CSR pathway.
  • This pathway generates IgE+ B cells and highlights a novel BCR-negative intermediate essential for CSR efficiency.