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Related Experiment Video

Updated: Jul 6, 2026

Isolation of Precursor B-cell Subsets from Umbilical Cord Blood
14:06

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Published on: April 16, 2013

Asynchronous replication and allelic exclusion in the immune system.

R Mostoslavsky1, N Singh, T Tenzen

  • 1Department of Cellular Biochemistry & Human Genetics, and Experimental Medicine & Cancer Research, PO Box 12272, Hebrew University, Jerusalem 91120, Israel.

Nature
|November 9, 2001
PubMed
Summary

Mature B cell development relies on allelic exclusion to select a single antigen receptor. DNA replication timing acts as an epigenetic mark, favoring early-replicating alleles for rearrangement, similar to X chromosome inactivation.

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Area of Science:

  • Immunology
  • Epigenetics
  • Molecular Biology

Background:

  • B cell development requires expressing a single antigen receptor, necessitating allelic exclusion.
  • Allelic exclusion ensures one receptor type is chosen from two available alleles.
  • Epigenetic mechanisms, potentially predating gene rearrangement, may govern allelic choice.

Purpose of the Study:

  • Investigate DNA replication timing as a mechanism for distinguishing between alleles.
  • Understand the epigenetic basis of allelic exclusion in B cell receptor gene loci.

Main Methods:

  • Analysis of DNA replication timing in B cell receptor (BCR) and T cell receptor (TCR) loci.
  • Examining asynchronous replication patterns in immune receptor genes.

Main Results:

  • B-cell-receptor loci (mu, kappa, lambda) and TCRbeta locus exhibit asynchronous replication.
  • This asynchronous replication pattern is established early in development and clonally maintained.
  • The early-replicating allele is preferentially selected for initial rearrangement.

Conclusions:

  • Asynchronous DNA replication serves as an epigenetic mark for allelic exclusion.
  • This process is crucial for selecting the initially rearranged allele in B cells.
  • Allelic exclusion in the immune system may share similarities with X chromosome inactivation.