Transient IL-7/IL-7R signaling provides a mechanism for feedback inhibition of immunoglobulin heavy chain gene rearrangements

Dipanjan Chowdhury, Ranjan Sen

Research output: Contribution to journalArticle

Abstract

Production of immunoglobulin heavy chain (IgH) protein feeds back to terminate further VH gene recombination, a phenomenon also referred to as allelic exclusion. Here we provide evidence to support the proposition that allelic exclusion is the consequence of terminating signals that activate VH genes for recombination. For the largest VHJ558 family of genes, this occurs by attenuating IL-7/IL-7R signals in pre-B cells. Loss of these signals reverts the VH locus to a chromatin state that is associated with hypoacetylated histones and is less accessible to nucleases. Furthermore, hyperacetylation and accessibility of unrearranged VH genes can be restored in allelically excluded splenic B cells by activating this pathway. Thus, transient signals mediate VH gene activation and inactivation during development.

Original languageEnglish (US)
Pages (from-to)229-241
Number of pages13
JournalImmunity
Volume18
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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