The Role of DNA Repair in Immunological Diversity: From Molecular Mechanisms to Clinical Ramifications

Peter Gullickson, Yunwen W. Xu, Laura J. Niedernhofer, Elizabeth L Thompson, Matthew Yousefzadeh

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


An effective humoral immune response necessitates the generation of diverse and high-affinity antibodies to neutralize pathogens and their products. To generate this assorted immune repertoire, DNA damage is introduced at specific regions of the genome. Purposeful genotoxic insults are needed for the successful completion of multiple immunological diversity processes: V(D)J recombination, class-switch recombination, and somatic hypermutation. These three processes, in concert, yield a broad but highly specific immune response. This review highlights the importance of DNA repair mechanisms involved in each of these processes and the catastrophic diseases that arise from DNA repair deficiencies impacting immune system function. These DNA repair disorders underline not only the importance of maintaining genomic integrity for preventing disease but also for robust adaptive immunity.

Original languageEnglish (US)
Article number834889
JournalFrontiers in immunology
StatePublished - Apr 1 2022

Bibliographical note

Funding Information:
This work is supported by funds from the NIH (U01 ES029603, R01 AG063543, P01 AG062413, and U19 AG056278) to LJN. ELT is supported by funds from the NIH T32 AG029796. MJY is supported by the Irene Diamond Fund/American Federation for Aging Research Postdoctoral Transition Award.

Publisher Copyright:
Copyright © 2022 Gullickson, Xu, Niedernhofer, Thompson and Yousefzadeh.


  • DNA damage
  • DNA repair
  • antibodies
  • immunodeficiency
  • immunological diversity


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