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Regulation of IgL Chain Recombination

Published on Jan 1, 2016
· DOI :10.1016/B978-0-12-374279-7.01008-0
Rena Levin-Klein5
Estimated H-index: 5
,
Yehudit Bergman36
Estimated H-index: 36
Abstract
The immunoglobulin light chain loci (Igκ and Igλ) are recombined via V(D)J recombination at the pre-B cell stage during B cell differentiation. The recombination process is highly regulated on multiple levels to ensure proper timing and locus specificity. In this article, we focus on a number of mechanisms which contribute to the tight control of the rearrangement, focusing on the Igκ locus, which is the primary IgL chain utilized in both mice and humans. We explain how regulation of locus accessibility, cellular signaling pathways, and transcription factor binding influence the recombination process. We also note regulation of the ‘allelic exclusion’ phenomenon, where only one B cell receptor is expressed in a single lymphocyte.
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  • Citations (1)
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References66
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Summary V(D)J recombination is initiated by a specialized transposase consisting of the subunits RAG-1 and RAG-2. The susceptibility of gene segments to DNA cleavage by the V(D)J recombinase is correlated with epigenetic modifications characteristic of active chromatin, including trimethylation of histone H3 on lysine 4 (H3K4me3). Engagement of H3K4me3 by a plant homeodomain (PHD) in RAG-2 promotes recombination in vivo and stimulates DNA cleavage by RAG in vitro. We now show that H3K4me3 acts a...
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The Igκ locus undergoes a variety of different molecular processes during B cell development, including V(D)J rearrangement and somatic hypermutations, which are influenced by cis regulatory regions (RR) within the locus. The Igκ locus includes three characterized RRs termed the intronic (iEκ), 3’Eκ and Ed enhancers. We had previously noted that a region of DNA upstream of the iEκ and matrix attachment region (MAR) was necessary for demethylation of the locus in cell culture. In this study, we f...
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#1Roberta Pelanda (University of Colorado Denver)H-Index: 31
Receptor editing, a major mechanism of B cell tolerance, can also lead to allelic inclusion at the immunoglobulin light chain loci and the development of B cells that coexpress two different immunoglobulin light chains and, therefore, two antibody specificities. Most allelically included B cells express two κ chains, although rare dual-λ cells are also observed. Moreover, these cells typically coexpress an autoreactive and a nonautoreactive antibody. Thus, allelically included B cells could oper...
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The mouse Igκ gene locus has three known transcriptional enhancers: an intronic enhancer (Ei), a 3′ enhancer (E3′), and a further downstream enhancer (Ed). We previously discovered, using the chromosome conformation-capture technique, that Ei and E3′ interact with a novel DNA sequence near the 3′ end of the Igκ locus, specifically in B cells. In the present investigation, we examined the function of this far downstream element. The sequence is evolutionarily conserved and exhibits a plasmacytoma...
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