Mechanisms for feedback inhibition of the immunoglobulin heavy chain locus

✍ Scribed by Dipanjan Chowdhury; Ranjan Sen

• Publisher: Elsevier Science
• Year: 2004
• Tongue: English
• Weight: 133 KB
• Volume: 16
• Category: Article
• ISSN: 0952-7915
• DOI: 10.1016/j.coi.2004.02.003

✦ Synopsis

The production of immunoglobulin heavy chain (IgH) protein in pro-B cells provides feedback to terminate further V H gene recombination. This phenomenon is referred to as allelic exclusion. The chromatin structure of the V H 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 V H genes (J558) and potentially activates these genes for recombination. Loss of these signals in the later stages of B-cell development reverts the V H J558 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 V H gene families. D-proximal V H genes, however, appear to be less susceptible to feedback inhibition.