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Review Open Access

Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)

  • Authors:
    • Yuxing Li
    • Yujiao Gong
    • Jiaxing Zhao
    • Rensen Ran
  • View Affiliations / Copyright

    Affiliations: School of Biological and Pharmaceutical Engineering, Lanzhou Jiaotong University, Lanzhou, Gansu 730070, P.R. China, Guangdong Provincial Engineering Research Center of Molecular Imaging, the Fifth Affiliated Hospital, Sun Yat‑sen University, Zhuhai, Guangdong 519000, P.R. China, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, P.R. China
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 68
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    Published online on: January 21, 2026
       https://doi.org/10.3892/ijmm.2026.5739
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Abstract

B‑lymphocytes (B‑cells) develop from hematopoietic stem cells in the bone marrow or fetal liver and differentiate into antibody‑secreting cells and memory B‑cells upon encountering antigens in peripheral lymphoid organs. Throughout this process, the expression of lineage‑associated genes is upregulated, whereas that of lineage‑inappropriate genes is repressed, thereby directing commitment to a specific B‑cell fate. Epigenetic regulatory mechanisms, including DNA methylation, post‑translational histone modifications and non‑coding RNAs, regulate gene transcription and play crucial roles in B‑cell development and differentiation. The dysregulation of these epigenetic processes may contribute to the pathogenesis of autoimmune diseases and B‑cell malignancies. Recent advances in high‑throughput techniques, including single‑cell RNA sequencing, chromatin immunoprecipitation‑sequencing and whole‑genome bisulfite sequencing, have significantly enhanced the understanding of epigenetic dysregulation in these disorders. The present review summarizes recent advances in the understanding of dysregulated epigenetic mechanisms underlying B‑cell‑mediated autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, primary Sjögren's syndrome, multiple sclerosis and type 1 diabetes mellitus) and lymphomas (such as diffuse large B‑cell lymphoma, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma and marginal zone lymphoma), and highlights emerging diagnostic biomarkers and therapeutic strategies.

View Figures

Figure 1

Major epigenetic mechanisms.
Chromatin remodeling is an ATP-dependent process that modulates
nucleosome architecture. DNA methylation is catalyzed by DNMTs and
removed by TETs. Histone acetylation is installed by HATs and
removed by HDACs. Histone methylation is catalyzed by HMTs and
reversed by KDMs. Histone ubiquitination is mediated through a
sequential cascade of E1 activating enzymes, E2 conjugating
enzymes, and E3 ligases, and is reversed by DUBs. miRNAs bind to
complementary sequences in target mRNAs, leading to transcript
degradation. DNMTs, DNA methyltransferases; TETs, ten-eleven
translocation enzymes; HATs, histone acetyltransferases; HDACs,
histone deacetylases; HMTs, histone methyltransferases; KDMs,
histone demethylases; DUBs, histone deubiquitinases; miRNA,
microRNA.

Figure 2

Roles of epigenetic regulators in
B-cell lymphopoiesis. HSC, hematopoietic stem cell; CLP, common
lymphoid progenitor; Pro-B cell, progenitor B cell; Pre-B cell,
precursor B cell; MBC, memory B cell; PC, plasma cell.

Figure 3

Schematic representation of
epigenetic dysregulation in B-cell lymphomas. Diffuse large B-cell
lymphoma primarily arises from activated or GC B cells;
representative epigenetic alterations include mutations in ARID1A,
KMT2D, CREBBP, TET2 and p300, and overexpression of HDAC1, HDAC2,
HDAC6, DNMT1, DNMT3B, EZH2, METTL3 and miR-155. Follicular lymphoma
originates from GC B cells; representative epigenetic alterations
include mutations in ARID1A, KMT2D, CREBBP, KMT2C, and p300,
overexpression of EZH2 and miR-155, and downregulation of TET1.
Mantle cell lymphoma mainly arises from mature B cells;
representative epigenetic changes include KMT2D mutations,
overexpression of DNMT1, HDACs, PRC2 components, and miR-155, and
downregulation of miR-26a. Burkitt lymphoma arises from GC B cells;
representative epigenetic alterations include overexpression of
DNMT1, DNMT3B and the miR-17-92 cluster, and downregulation of
miR-150, miR-155, and members of the let-7 family. Marginal zone
lymphoma originates from mature B cells; representative epigenetic
dysregulation includes recurrent mutations in ARID1A, KMT2D,
CREBBP, and p300, overexpression of miR-555, miR-221 and miR-29c,
and downregulation of miR-532-5p. In the image, the upward arrows
(↑) indicate an increased expression and the downward arrows (↓)
indicate a decreased expression.
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Copy and paste a formatted citation
Spandidos Publications style
Li Y, Gong Y, Zhao J and Ran R: <p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>. Int J Mol Med 57: 68, 2026.
APA
Li, Y., Gong, Y., Zhao, J., & Ran, R. (2026). <p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>. International Journal of Molecular Medicine, 57, 68. https://doi.org/10.3892/ijmm.2026.5739
MLA
Li, Y., Gong, Y., Zhao, J., Ran, R."<p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>". International Journal of Molecular Medicine 57.3 (2026): 68.
Chicago
Li, Y., Gong, Y., Zhao, J., Ran, R."<p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>". International Journal of Molecular Medicine 57, no. 3 (2026): 68. https://doi.org/10.3892/ijmm.2026.5739
Copy and paste a formatted citation
x
Spandidos Publications style
Li Y, Gong Y, Zhao J and Ran R: <p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>. Int J Mol Med 57: 68, 2026.
APA
Li, Y., Gong, Y., Zhao, J., & Ran, R. (2026). <p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>. International Journal of Molecular Medicine, 57, 68. https://doi.org/10.3892/ijmm.2026.5739
MLA
Li, Y., Gong, Y., Zhao, J., Ran, R."<p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>". International Journal of Molecular Medicine 57.3 (2026): 68.
Chicago
Li, Y., Gong, Y., Zhao, J., Ran, R."<p>Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review)</p>". International Journal of Molecular Medicine 57, no. 3 (2026): 68. https://doi.org/10.3892/ijmm.2026.5739
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