Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin κ-chain locus

被引：0
作者：
Shira Fraenkel
Raul Mostoslavsky
Tatiana I Novobrantseva
Roberta Pelanda
Jayanta Chaudhuri
Gloria Esposito
Steffen Jung
Frederick W Alt
Klaus Rajewsky
Howard Cedar
Yehudit Bergman
机构：
[1] The Hebrew University Hadassah Medical School,The Center for Blood Research and Department of Genetics
[2] Howard Hughes Medical Institute,Department of Immunology
[3] The Children's Hospital,undefined
[4] Harvard University Medical School,undefined
[5] Institute for Genetics,undefined
[6] University of Cologne,undefined
[7] Alnylam Pharmaceuticals,undefined
[8] National Jewish Medical and Research Center,undefined
[9] Memorial Sloan Kettering Cancer Center,undefined
[10] Artemis Pharmaceuticals,undefined
[11] Weizmann Institute of Science,undefined
[12] Center for Blood Research,undefined
[13] Harvard Medical School,undefined
来源：
Nature Immunology | 2007年 / 8卷
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摘要：
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.
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页码：715 / 722
页数：7
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