A stepwise epigenetic process controls immunoglobulin allelic exclusion

  title={A stepwise epigenetic process controls immunoglobulin allelic exclusion},
  author={Yehudit Bergman and Howard Cedar},
  journal={Nature Reviews Immunology},
During the differentiation of T and B cells, immune-receptor loci in the genome must be made sterically accessible so that they can undergo rearrangement. Here, we discuss how this is carried out by the stepwise removal of epigenetic repression mechanisms — such as later-replication timing, heterochromatization, histone hypo-acetylation and DNA methylation — in a manner that initially favours one allele in each cell. We propose that this mechanism of allelic exclusion might also be the basis… 

Epigenetic control of recombination in the immune system.

Choreography of Ig allelic exclusion.

Variability and Exclusion in Host and Parasite: Epigenetic Regulation of Ig and var Expression1

The similarities as well as the unique characteristics of the epigenetic mechanisms involved in the establishment of mutually exclusive expression in the immune and parasite systems are discussed.

Regulation of antigen receptor gene assembly by genetic-epigenetic crosstalk.

Allelic exclusion of immunoglobulin genes: models and mechanisms

The theoretical models that have been proposed to explain the establishment of Ig allelic exclusion are reviewed and the molecular mechanisms utilized by developing B cells to ensure the monoallelic expression of Igκ and Igλ light chain genes are focused on.

Epigenetic control in the immune response.

Lymphocytes are, thus, becoming a tractable system for genetic and biochemical dissection of the ways in which the genome is embedded with regulatory information to achieve developmental complexity.

Igκ allelic inclusion is a consequence of receptor editing

It is demonstrated that B lymphocytes carrying two B-cell receptors are recruited to germinal center reactions, and thus fully participate in humoral immune responses, and provide a mechanism whereby autoreactive B cells might “escape” central tolerance.

Epigenetics of antigen-receptor gene assembly.

  • C. Murre
  • Biology
    Current opinion in genetics & development
  • 2007

Transcription of productive and nonproductive VDJ‐recombined alleles after IgH allelic exclusion

After the establishment of IgH allelic exclusion, monoallelic recruitment to heterochromatin does not silence VDJ‐ or DJ‐transcription, but serves another purpose.



Asynchronous replication and allelic exclusion in the immune system

It is shown that all of the B-cell-receptor loci and the TCRβ locus replicate asynchronously, indicating that allelic exclusion in the immune system may be very similar to the process of X chromosome inactivation.

Differential accessibility at the κ chain locus plays a role in allelic exclusion

It is demonstrated that epigenetic and chromatin changes actually occur on one allele with a higher probability than the other in a model system in which rearrangement of the endogenous immunoglobulin κ locus is prevented.

Monoallelic gene expression: a repertoire of recurrent themes

The unifying features among these monoallelically expressed systems and the unique characteristics displayed by each of them are discussed.

A multistep mechanism for the activation of rearrangement in the immune system

It is shown that DNA methylation brings about histone underacetylation, histone H3(K9) methylation, DNaseI resistance, and strong inhibition of both transcription and recombination in dividing cells.

Targeted inhibition of V(D)J recombination by a histone methyltransferase

It is demonstrated that a histone methyltransferase overrides accessibility control element function and cripples V(D)J recombination of chromosomal gene segments, indicating a key function in the tissue- and stage-specific suppression of antigen receptor gene assembly during lymphocyte development.

Kappa chain monoallelic demethylation and the establishment of allelic exclusion.

Evidence is provided suggesting that the initial establishment of allelic exclusion involves differential availability of the two kappa alleles for rearrangement, and that demethylation may actually underly the process of allelelic exclusion by directing the initial choice of a single kappa allele for rearranges.