T-box transcription factor T-bet, a key player in a unique type of B-cell activation essential for effective viral clearance
Open accessAbstract
Significance: Here, we show that signals delivered by antigen engagement, IFNγ, and toll-like receptor 7 [TLR7] induce T-box transcription factor T-bet and IgG2a switching in B cells. The IgG2a product of these signals is important for viral immunity. For example, the titers of mouse gammaherpesvirus 68, an Epstein–Barr-related virus, are not well reduced if the B cells cannot express T-bet and consequently cannot switch to production of IgG2a. The T-bet expressing B cells resemble a subset of B cells that appears in autoimmune prone mice and women. Thus, a B-cell differentiation pathway that has evolved to promote immunity to viruses may also contribute to autoimmunity.
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Treg depletion is expected to promote a chronic low-grade inflammatory milieu characterized by elevated interferon γ, and such a cytokine environment is well-suited to sustain T-bet+ ABC-like populations.
“their depletion is expected to promote a chronic low-grade inflammatory milieu characterized by elevated interferon γ [69], such a cytokine environment is well-suited to sustain T-bet+ ABC-like populations [70].”
From PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain (2026) · cites this paper as [70]
Cites
Control of Effector CD8 <sup>+</sup> T Cell Function by the Transcription Factor <i>Eomesodermin</i>
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T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells
Lighvani, A. A., Frucht, D. M., Jankovic, D., Yamane, H., Aliberti, J., Hissong, B. D., Nguyen, B. V., Gadina, M., Sher, A., Paul, W. E., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261570598 · Cited by 783 · see citing works
A B-cell subset uniquely responsive to innate stimuli accumulates in aged mice
Hao, Y., O'Neill, P., Naradikian, M. S., Scholz, J. L., & Cancro, M. P. (2011) · Blood · doi:10.1182/blood-2011-01-330530 · Cited by 622 · see citing works
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Functional SARS-CoV-2-Specific Immune Memory Persists after Mild COVID-19
Rodda, L. B., Netland, J., Shehata, L., Pruner, K. B., Morawski, P. A., Thouvenel, C. D., Takehara, K. K., Eggenberger, J., Hemann, E. A., Waterman, H. R., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.029 · Cited by 647 · see citing works
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Age-Associated B Cells: A T-bet–Dependent Effector with Roles in Protective and Pathogenic Immunity
Rubtsova, K., Rubtsov, A. V., Cancro, M. P., & Marrack, P. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1501209 · Cited by 246 · see citing works
Self-citationAge-associated B cells in autoimmune diseases
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Cell signaling and the aging of B cells
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- Authors
- Rubtsova, K., Rubtsov, A. V., van Dyk, L. F., Kappler, J. W., & Marrack, P.
- Affiliations
- Howard Hughes Medical Institute (US)
- Department of Immunology, National Jewish Health and University of Colorado Health Sciences Center, Denver, CO 80206;
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-06
- Volume
- 110
- Issue
- 34
- Pages
- E3216-24
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3752276
- OpenAlex
- W2089017798
- Cited by
- 300
- References
- 3
- Citations by year
- 2026: 17 · 2025: 27 · 2024: 26 · 2023: 30 · 2022: 34 · 2021: 42 · 2020: 27 · 2019: 27 · 2018: 16 · 2017: 27 · 2016: 11 · 2015: 8 · 2014: 8
- FWCI
- 4.97
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- other-oa
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Cancer Institute (R01CA168558, R01CA103632)
- National Institute of Allergy and Infectious Diseases (AI-18785, AI 22295, P01AI022295, T32AI074491, R37AI018785, R56AI018785, AI074491, R01AI018785)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T-bet, T-box transcription factor, B cell activation, IgG2a, antibody isotype switching, TLR7, interferon-gamma receptor, B cell receptor, CD11b, CD11c, antiviral immunity, viral clearance, autoimmunity, B-1 cells
- MeSH terms
- Interferon gamma Receptor, T-bet Transcription Factor, Animals, B-Lymphocytes, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Herpesviridae Infections, Immunoglobulin G, Lymphocyte Activation, Membrane Glycoproteins, Mice, Inbred C57BL, Autoimmunity, Receptors, Interferon, DNA Primers, Gammaherpesvirinae, Mice, Knockout, T-Box Domain Proteins, Toll-Like Receptor 7, Mice, Real-Time Polymerase Chain Reaction
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