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Cited by 189T-cell and B-cell ImmunologySystemic Lupus Erythematosus ResearchGenomics and Chromatin Dynamics

IFNγ induces epigenetic programming of human T-bethi B cells and promotes TLR7/8 and IL-21 induced differentiation

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Zumaquero, Esther, Stone, Sara L, Scharer, Christopher D, Jenks, Scott A, Nellore, Anoma, Mousseau, Betty, Rosal-Vela, Antonio, Botta, Davide +13 more·2019·eLife
DOI 10.7554/elife.41641PMC PMC6544433

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Abstract

Although B cells expressing the IFNγR or the IFNγ-inducible transcription factor T-bet promote autoimmunity in Systemic Lupus Erythematosus (SLE)-prone mouse models, the role for IFNγ signaling in human antibody responses is unknown. We show that elevated levels of IFNγ in SLE patients correlate with expansion of the T-bet expressing IgDnegCD27negCD11c+CXCR5neg (DN2) pre-antibody secreting cell (pre-ASC) subset. We demonstrate that naïve B cells form T-bethi pre-ASCs following stimulation with either Th1 cells or with IFNγ, IL-2, anti-Ig and TLR7/8 ligand and that IL-21 dependent ASC formation is significantly enhanced by IFNγ or IFNγ-producing T cells. IFNγ promotes ASC development by synergizing with IL-2 and TLR7/8 ligands to induce genome-wide epigenetic reprogramming of B cells, which results in increased chromatin accessibility surrounding IRF4 and BLIMP1 binding motifs and epigenetic remodeling of IL21R and PRDM1 loci. Finally, we show that IFNγ signals poise B cells to differentiate by increasing their responsiveness to IL-21.

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  • ABCs are characterized by distinct gene expression profiles with expression of transcription factors T-BET, IRF5, and ZEB2.

    “ABCs are characterized by their distinct gene expression profiles with the expression of a set a transcription factor including T-BET, IRF5, and ZEB2 [73 -75].”

    From Is there a role for B cells in Alzheimer's disease? (2026) · cites this paper as [75]

    The Results section on T-bet-high B cells reports a distinct gene-expression profile and higher TBX21 (T-BET) expression; page numbers are unavailable in our copy. It does not establish IRF5 or ZEB2 expression as features of these cells. Searches for both factors found no supporting passage. (LLM, conf=0.86)

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Cited by

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Authors
Zumaquero, E., Stone, S. L., Scharer, C. D., Jenks, S. A., Nellore, A., Mousseau, B., Rosal-Vela, A., Botta, D., Bradley, J. E., Wojciechowski, W., Ptacek, T., Danila, M. I., Edberg, J. C., Bridges, S. L., Kimberly, R. P., Chatham, W. W., Schoeb, T. R., Rosenberg, A. F., Boss, J. M., Sanz, I., & Lund, F. E.
Affiliations
  • University of Alabama at Birmingham (US)
  • Emory University (US)
  • Department of Microbiology, The University of Alabama at Birmingham, Birmingham, United States
  • University of Rochester Medicine (US)
  • Department of Medicine, Division of Rheumatology, Emory University, Atlanta, United States
Corresponding author
Lund, Frances E
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2019-05-15
Volume
8
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.41641
PMC
PMC6544433
OpenAlex
W2949788114
Cited by
189
References
2
Citations by year
2026: 33 · 2025: 23 · 2024: 21 · 2023: 32 · 2022: 25 · 2021: 29 · 2020: 19 · 2019: 6
FWCI
7.88
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • RODIN (Universidad de Cádiz) (submittedVersion, other-oa)
Funders
  • National Institutes of Health (UL1 TR001417, 1P30 DK079337, P01 AI078907, R01 AI110508, R01 AI123733, P01 AI125180, R37 AI049660, U19 AI110483, T32 GM008361, K23 AR062100)
  • Lupus Research Alliance (#550070)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
interferon-gamma, T-bet, B cell differentiation, epigenetic reprogramming, chromatin accessibility, IL-21, interleukin-2, IRF4, Blimp-1, interleukin-21 receptor, systemic lupus erythematosus, autoimmunity, antibody response, Th1 cells, naive B cells
MeSH terms
Interleukin-21, T-bet Transcription Factor, Cell Differentiation, Humans, Interferon-gamma, Interleukins, Lupus Erythematosus, Systemic, B-Lymphocyte Subsets, T-Box Domain Proteins, Epigenesis, Genetic, Toll-Like Receptor 7, Toll-Like Receptor 8, Gene Regulatory Networks

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