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Epigenetics of the antibody response

Journal

TRENDS IN IMMUNOLOGY
Volume 34, Issue 9, Pages 460-470

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.it.2013.03.006

Keywords

AID; antibody; autoimmunity; B cell; Blimp-1; CSR; epigenetic; immunoglobulin; memory B cell; neoplasia; plasma cell; SHM

Categories

Funding

  1. U.S. National Institutes of Health [AI 079705, AI 045011, AI 105813, AI 060573]
  2. Arthritis National Research Foundation

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Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and miRNAs modulate the expression of critical elements of that machinery, such as activation-induced cytidine deaminase (AID), as well as factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1). These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such as those targeted in autoimmunity, and B cell neoplasia

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