Epigenetics of the antibody and autoantibody response

Justin B. Moroney, Daniel P. Chupp, Zhenming Xu, Hong Zan, Paolo Casali

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

B cell differentiation driven by microbial antigens leads to production of anti-microbial antibodies, such as those neutralizing viruses, bacteria or bacterial toxin, that are class-switched (IgG and IgA) and somatically hypermutated (maturation of the antibody response) as well as secreted in large volume by plasma cells. Similar features characterize pathogenic antibodies to self-antigens in autoimmunity, reflecting the critical role of class switch DNA recombination (CSR), somatic hypermutation (SHM) and plasma cell differentiation in the generation of antibodies to not only foreign antigens but also self-antigens (autoantibodies). Central to CSR/SHM and plasma cell differentiation are AID, a potent DNA cytidine deaminase encoded by Aicda, and Blimp-1, a transcription factor encoded by Prdm1. B cell-intrinsic expression of Aicda and Prdm1 is regulated by epigenetic elements and processes, including DNA methylation, histone post-translational modifications and non-coding RNAs, particularly miRNAs. Here, we will discuss: B cell-intrinsic epigenetic processes that regulate antibody and autoantibody responses; how epigenetic dysregulation alters CSR/SHM and plasma cell differentiation, thereby leading to autoantibody responses, as in systemic lupus; and, how these can be modulated by nutrients, metabolites, and hormones through changes in B cell-intrinsic epigenetic mechanisms, which can provide therapeutic targets in autoimmunity.

Original languageEnglish (US)
Pages (from-to)75-86
Number of pages12
JournalCurrent Opinion in Immunology
Volume67
DOIs
StatePublished - Dec 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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