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Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells

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  • Justin B. Moroney

    (Immunology & Molecular Genetics, University of Texas Long School of Medicine, UT Health Science Center)

  • Anusha Vasudev

    (Immunology & Molecular Genetics, University of Texas Long School of Medicine, UT Health Science Center)

  • Alexander Pertsemlidis

    (Greehey Children’s Cancer Research Institute, University of Texas Long School of Medicine, UT Health Science Center)

  • Hong Zan

    (Immunology & Molecular Genetics, University of Texas Long School of Medicine, UT Health Science Center)

  • Paolo Casali

    (Immunology & Molecular Genetics, University of Texas Long School of Medicine, UT Health Science Center)

Abstract

Memory B cells (MBCs) are long-lived and produce high-affinity, generally, class-switched antibodies. Here, we use a multiparameter approach involving CD27 to segregate naïve B cells (NBC), IgD+ unswitched (unsw)MBCs and IgG+ or IgA+ class-switched (sw)MBCs from humans of different age, sex and race. Conserved antibody variable gene expression indicates that MBCs emerge through unbiased selection from NBCs. Integrative analyses of mRNAs, miRNAs, lncRNAs, chromatin accessibility and cis-regulatory elements uncover a core mRNA-ncRNA transcriptional signature shared by IgG+ and IgA+ swMBCs and distinct from NBCs, while unswMBCs display a transitional transcriptome. Some swMBC transcriptional signature loci are accessible but not expressed in NBCs. Profiling miRNAs reveals downregulated MIR181, and concomitantly upregulated MIR181 target genes such as RASSF6, TOX, TRERF1, TRPV3 and RORα, in swMBCs. Finally, lncRNAs differentially expressed in swMBCs cluster proximal to the IgH chain locus on chromosome 14. Our findings thus provide new insights into MBC transcriptional programs and epigenetic regulation, opening new investigative avenues on these critical cell elements in human health and disease.

Suggested Citation

  • Justin B. Moroney & Anusha Vasudev & Alexander Pertsemlidis & Hong Zan & Paolo Casali, 2020. "Integrative transcriptome and chromatin landscape analysis reveals distinct epigenetic regulations in human memory B cells," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19242-6
    DOI: 10.1038/s41467-020-19242-6
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    Cited by:

    1. Kathryn Weinand & Saori Sakaue & Aparna Nathan & Anna Helena Jonsson & Fan Zhang & Gerald F. M. Watts & Majd Al Suqri & Zhu Zhu & Deepak A. Rao & Jennifer H. Anolik & Michael B. Brenner & Laura T. Don, 2024. "The chromatin landscape of pathogenic transcriptional cell states in rheumatoid arthritis," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    2. Yijiang Xu & Hang Zhou & Ginell Post & Hong Zan & Paolo Casali, 2022. "Rad52 mediates class-switch DNA recombination to IgD," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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