Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin κ-chain locus Journal Article
| Authors: | Fraenkel, S.; Mostoslavsky, R.; Novobrantseva, T. I.; Pelanda, R.; Chaudhuri, J.; Esposito, G.; Jung, S.; Alt, F. W.; Rajewsky, K.; Cedar, H.; Bergman, Y. |
| Article Title: | Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin κ-chain locus |
| Abstract: | Monoallelic demethylation and rearrangement control allelic exclusion of the immunoglobulin κ-chain locus (Igk locus) in B cells. Here, through the introduction of pre-rearranged Igk genes into their physiological position, the critical rearrangement step was bypassed, thereby generating mice producing B cells simultaneously expressing two different immunoglobulin-κ light chains. Such 'double-expressing' B cells still underwent monoallelic demethylation at the Igk locus, and the demethylated allele was the 'preferred' substrate for somatic hypermutation in each cell. However, methylation itself did not directly inhibit the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development. |
| Keywords: | controlled study; nonhuman; animal cell; mouse; animals; mice; allele; animal tissue; gene expression; cell maturation; gene locus; genetic variability; alleles; in vivo study; in vitro study; dna methylation; b lymphocyte; b-lymphocytes; mice, transgenic; somatic hypermutation; gene rearrangement; immunoglobulin variable region; epigenetics; epigenesis, genetic; cellular distribution; immunoglobulin kappa chain; immunoglobulin kappa-chains; enzyme mechanism; genetic markers; gene location; cytidine; demethylation; somatic hypermutation, immunoglobulin; deaminase; antibody diversity; gene rearrangement, b-lymphocyte |
| Journal Title: | Nature Immunology |
| Volume: | 8 |
| Issue: | 7 |
| ISSN: | 1529-2908 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2007-07-01 |
| Start Page: | 715 |
| End Page: | 722 |
| Language: | English |
| DOI: | 10.1038/ni1476 |
| PUBMED: | 17546032 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 16" - "Export Date: 17 November 2011" - "CODEN: NIAMC" - "Source: Scopus" |
