Misregulation of the IgH Locus in Thymocytes

Functional antigen receptor genes are assembled by somatic rearrangements that are largely lymphocyte lineage specific. The immunoglobulin heavy chain ( ) gene locus is unique amongst the seven antigen receptor loci in undergoing partial gene rearrangements in the wrong lineage. Here we demonstrate...

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Bibliographic Details
Published in:Frontiers in immunology 2018-11, Vol.9, p.2426-2426
Main Authors: Kumari, Gita, Gerasimova, Tatiana, Du, Hansen, De, Supriyo, Wood, 3rd, William H, Becker, Kevin G, Sen, Ranjan
Format: Article
Language:English
Subjects:
B cells
chromatin
enhancer
IgH locus
Immunology
thymocytes
VDJ recombination
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Summary:Functional antigen receptor genes are assembled by somatic rearrangements that are largely lymphocyte lineage specific. The immunoglobulin heavy chain ( ) gene locus is unique amongst the seven antigen receptor loci in undergoing partial gene rearrangements in the wrong lineage. Here we demonstrate that breakdown of lineage-specificity is associated with inappropriate activation of the Eμ enhancer during T cell development by a different constellation of transcription factors than those used in developing B cells. This is reflected in reduced enhancer-induced epigenetic changes, eRNAs, formation of the RAG1/2-rich recombination center, attenuated chromatin looping and markedly different utilization of D gene segments in CD4 CD8 (DP) thymocytes. Additionally, CTCF-dependent V locus compaction is disrupted in DP cells despite comparable transcription factor binding in both lineages. These observations identify multiple mechanisms that contribute to lineage-specific antigen receptor gene assembly.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2018.02426