Dissecting Epigenetic Dysregulation of Primary Antibody Deficiencies

J Clin Immunol. 2016 May:36 Suppl 1:48-56. doi: 10.1007/s10875-016-0267-4. Epub 2016 Mar 17.

Abstract

Primary antibody deficiencies (PADs), the most prevalent inherited primary immunodeficiencies (PIDs), are associated with a wide range of genetic alterations (both monogenic or polygenic) in B cell-specific genes. However, correlations between the genotype and clinical manifestations are not evident in all cases indicating that genetic interactions, environmental and epigenetic factors may have a role in PAD pathogenesis. The recent identification of key defects in DNA methylation in common variable immunodeficiency as well as the multiple evidences on the role of epigenetic control during B cell differentiation, activation and during antibody formation highlight the importance of investing research efforts in dissecting the participation of epigenetic defects in this group of diseases. This review focuses on the role of epigenetic control in B cell biology which can provide clues for the study of potential novel pathogenic defects involved in PADs.

Keywords: B lymphocytes; DNA methylation; Epigenetics; Histone modifications; Primary Antibody Deficiencies; Primary Immunodeficiencies.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinemia / genetics*
  • Agammaglobulinemia / immunology*
  • Agammaglobulinemia / metabolism
  • Animals
  • Antibody Affinity / genetics
  • Antibody Affinity / immunology
  • Antibody Formation / genetics
  • Antibody Formation / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • DNA Methylation
  • Epigenesis, Genetic*
  • Gene Expression Regulation*
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Histones / metabolism
  • Humans
  • Immunologic Deficiency Syndromes / genetics
  • Immunologic Deficiency Syndromes / immunology
  • Immunologic Deficiency Syndromes / metabolism
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Mutation
  • Plasma Cells / cytology
  • Plasma Cells / immunology
  • Plasma Cells / metabolism

Substances

  • Histones