Elsevier

Clinical Immunology

Volume 222, January 2021, 108622
Clinical Immunology

Review Article
DNA methylation signatures of autoimmune diseases in human B lymphocytes

https://doi.org/10.1016/j.clim.2020.108622Get rights and content
Under a Creative Commons license
open access

Highlights

  • B lymphocyte subsets exhibit distinctive DNA methylation patterns.

  • Dynamic differential DNA methylation underlies normal B cell differentiation.

  • DNA methylation limits B cell activation and differentiation.

  • Differentially methylated sites stratify autoimmune from control subjects.

  • Editing DNA methylation tools in the mammalian genome have potential translational applications.

Abstract

B lymphocytes play key roles in adaptive and innate immunity. In autoimmune diseases, their participation in disease instigation and/or progression has been demonstrated in both experimental models and clinical trials. Recent epigenetic investigations of human B lymphocyte subsets revealed the importance of DNA methylation in exquisitely regulating the cellular activation and differentiation programs. This review discusses recent advances on the potential of DNA methylation to shape events that impart generation of plasma cells and memory B cells, providing novel insight into homeostatic regulation of the immune system. In parallel, epigenetic profiling of B cells from patients with systemic or organo-specific autoimmune diseases disclosed distinctive differential methylation regions that, in some cases, could stratify patients from controls. Development of tools for editing DNA methylation in the mammalian genome could be useful for future functional studies of epigenetic regulation by offering the possibility to edit locus-specific methylation, with potential translational applications.

Keywords

DNA methylation
Autoimmunity
B lymphocyte
Crohn's disease
Inflammatory bowel disease
Multiple sclerosis
Rheumatoid arthritis
Sjögren's syndrome
Systemic lupus erythematosus
Ulcerative colitis

Abbreviations

5mC
5-methylcytosine
AICDA
activation-induced cytidine deaminase
BLNK
B cell Linker
CD
Crohn's disease
CSF
cerebrospinal fluid
DNMT
DNA methyltransferase
ERK
extracellular signal-regulated kinase
IAP
intracisternal A particle
IBD
Inflammatory bowel disease
IFI44L
interferon-induced protein 44-like
IGF2
insulin-like growth factor 2
LT-a
lymphotoxin alpha
MeCP2
methyl-CpG-binding protein
MS
multiple sclerosis
PBMC
peripheral blood mononuclear cells
RA
rheumatoid arthritis
RRMS
remitting relapsing forms of MS
TCE
trichloroethylene
TMPD
tetramethylpentadecane
TSS
transcriptional start site
SAH
S-adenosylhomocysteine
SAM
S-adenosylmethionine
SLE
Systemic lupus erythematosus
UC
ulcerative colitis
UV
ultraviolet

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