Allelic exclusion of the immunoglobulin heavy chain locus is independent of its nuclear localization in mature B cells

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Abstract

In developing B cells, the immunoglobulin heavy chain (IgH) locus is thought to move from repressive to permissive chromatin compartments to facilitate its scheduled rearrangement. In mature B cells, maintenance of allelic exclusion has been proposed to involve recruitment of the non-productive IgH allele to pericentromeric heterochromatin. Here, we used an allele-specific chromosome conformation capture combined with sequencing (4C-seq) approach to unambigously follow the individual IgH alleles in mature B lymphocytes. Despite their physical and functional difference, productive and non-productive IgH alleles in B cells and unrearranged IgH alleles in T cells share many chromosomal contacts and largely reside in active chromatin. In brain, however, the locus resides in a different repressive environment. We conclude that IgH adopts a lymphoid-specific nuclear location that is, however, unrelated to maintenance of allelic exclusion. We additionally find that in mature B cells-but not in T cells-the distal VH regions of both IgH alleles position themselves away from active chromatin. This, we speculate, may help to restrict enhancer activity to the productively rearranged VH promoter element.

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APA

Holwerda, S. J. B., Van De Werken, H. J. G., Ribeiro De Almeida, C., Bergen, I. M., De Bruijn, M. J. W., Verstegen, M. J. A. M., … De Laat, W. (2013). Allelic exclusion of the immunoglobulin heavy chain locus is independent of its nuclear localization in mature B cells. Nucleic Acids Research, 41(14), 6905–6916. https://doi.org/10.1093/nar/gkt491

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