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Front. Immunol. | doi: 10.3389/fimmu.2018.00355

Epigenomic modifications mediating antibody maturation

  • 1University of Exeter, United Kingdom
  • 2Sheffield Hallam University, United Kingdom

Epigenetic modifications, such as histone modifications, DNA methylation status, and non-coding RNAs (ncRNA) all contribute to antibody maturation during somatic hypermutation (SHM) and class switch recombination (CSR). Histone modifications alter the chromatin landscape and, together with DNA primary and tertiary structures, they help recruit Activation-Induced Cytidine Deaminase (AID) to the immunoglobulin (Ig) locus. AID is a potent DNA mutator, which catalyses cytosine-to-uracil deamination on single-stranded DNA to create U:G mismatches. It has been shown that alternate chromatin modifications, in concert with ncRNAs and potentially DNA methylation, regulate AID recruitment and stabilise DNA repair factors. We hereby assess the combination of these distinct modifications and discuss how they contribute to initiating differential DNA repair pathways at the Ig locus, which ultimately leads to enhanced antibody-antigen binding affinity (SHM) or antibody isotype switching (CSR). We will also highlight how misregulation of epigenomic regulation during DNA repair can compromise antibody development, and lead to a number of immunological syndromes and cancer.

Keywords: epigenetic modifications, epigenomics and epigenetics, Antibody Diversity, Cytosine deamination, somatic hypermutation (SHM), class switch recombination (CSR), B cell maturation

Received: 27 Nov 2017; Accepted: 08 Feb 2018.

Edited by:

Deborah K. Dunn-Walters, University of Surrey, United Kingdom

Reviewed by:

Anne Corcoran, Babraham Institute, United Kingdom
David J. Fear, King's College London, United Kingdom  

Copyright: © 2018 Sheppard, Morrish, Dillon, Leyland and Chahwan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Richard Chahwan, University of Exeter, Stocker Road, Exeter, EX4 4QD, United Kingdom, r.chahwan@ex.ac.uk