Mechanisms for feedback inhibition of the immunoglobulin heavy chain locus

Dipanjan Chowdhury, Ranjan Sen

Research output: Contribution to journalArticle

Abstract

The production of immunoglobulin heavy chain (IgH) protein in pro-B cells provides feedback to terminate further VH gene recombination. This phenomenon is referred to as allelic exclusion. The chromatin structure of the VH genes regulates their recombination potential, hence alterations in chromatin are a key factor in allelic exclusion. In pro-B cells, IL-7/IL-7R signaling induces histone hyperacetylation and nuclease accessibility of the largest family of VH genes (J558) and potentially activates these genes for recombination. Loss of these signals in the later stages of B-cell development reverts the VHJ558 gene segments to a less accessible state, making them recombinationally refractive. This provides a molecular mechanism for allelic exclusion of these genes. Similar transient signals may be responsible for enforcing allelic exclusion in other VH gene families. D-proximal VH genes, however, appear to be less susceptible to feedback inhibition.

Original languageEnglish (US)
Pages (from-to)235-240
Number of pages6
JournalCurrent Opinion in Immunology
Volume16
Issue number2
DOIs
StatePublished - Apr 2004
Externally publishedYes

Keywords

  • B-cell receptor
  • BCR
  • D
  • Diversity gene segment
  • ERK
  • Extracellular signal-related kinase
  • H
  • Heavy
  • Ig
  • IL
  • Immune receptor tyrosine-based activation motif
  • Immunoglobulin
  • Interleukin
  • ITAM
  • J
  • Joining gene segment
  • L
  • Light
  • MAPK
  • Mitogen-activated protein kinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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