Critical role for Stat3 in T-dependent terminal differentiation of IgG B cells
Open accessAbstract
Stat proteins are latent cytoplasmic transcription factors that are crucial in many aspects of mammalian development. In the immune system, Stat3 has distinct roles in T-cell, neutrophil, and macrophage function, but a role for Stat3 in B-cell development, particularly in the terminal differentiation of B cells into antibody-secreting plasma cells, has never been directly tested. In this study, we used the Cre/lox system to generate a mouse strain in which Stat3 was conditionally deleted in the B-cell lineage (Stat3fl/flCD19Cre/+). B-cell development, establishment of the peripheral B-cell compartment, and baseline serum antibody levels were unperturbed in Stat3fl/flCD19Cre/+ mice. Strikingly, Stat3fl/flCD19Cre/+ mice displayed profound defects in T-dependent (TD) IgG responses, but normal TD IgM, IgE, and IgA responses and T-independent (TI) IgM and IgG3 responses. In addition, germinal center (GC) formation, isotype switching, and generation of memory B cells, including IgG+ memory cells, were all intact in Stat3fl/flCD19Cre/+ mice, indicating that the requirement for Stat3 was limited to plasma cell differentiation. These results demonstrate a profound yet highly selective role for Stat3 in TD IgG plasma cell differentiation, and therefore represent a unique example of a transcription factor regulating isotype-specific terminal B-cell differentiation.
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B cell-specific STAT3 knockout reduces B cell compartments and plasma cells.
“Reduced B cell compartments and plasma cells”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Fornek et al., 2006
The discussion reports a profound decrease in T-dependent IgG antibody-secreting cells after B-cell-specific Stat3 deletion, supporting a reduction in that plasma-cell subset. It also states that B-cell numbers in the bone marrow, spleen, and lymph nodes were equivalent to controls and that B-cell development was intact, contrary to the claimed reduction in B-cell compartments. (LLM, conf=0.90)
Experimental — accuracy not yet measuredT cell-secreted IL-21 activates STAT3, which facilitates differentiation of later-stage B-lineage-committed CD19+ precursors to IgG-secreting plasma cells.
“T cell–secreted IL-21 activates STAT3, which facilitates differentiation of later-stage B-lineage–committed CD19+ precursors to IgG-secreting plasma cells”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Fornek et al., 2006
The Introduction (page not supplied) says IL-21 activates STAT3, and the Discussion proposes that STAT3 activation helps drive T-dependent IgG plasma-cell formation. But the Discussion names IL-21 as one of several possible cytokines, rather than establishing that T-cell-secreted IL-21 drives this process. The paper studies CD19-lineage B cells, not specifically later-stage CD19+ precursors. (LLM, conf=0.87)
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- Authors
- Fornek, J. L., Tygrett, L. T., Waldschmidt, T. J., Poli, V., Rickert, R. C., & Kansas, G. S.
- Affiliations
- Northwestern University (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2006-02-01
- Volume
- 107
- Issue
- 3
- Pages
- 1085-1091
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1895906
- OpenAlex
- W2054039779
- Cited by
- 148
- References
- 33
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 2 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 7 · 2019: 8 · 2018: 12 · 2017: 4 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 7 · 2012: 8
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- American Cancer Society
- Concern Foundation
- Ministero dell’Istruzione, dell’Università e della Ricerca
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (AA-014400, R01AA014400)
- National Institute of General Medical Sciences (GM08061)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Keywords
- STAT3, plasma cell differentiation, B cell terminal differentiation, germinal center, class switch recombination, memory B cells, T cell-dependent immunity, B cell development
- MeSH terms
- Animals, Cell Differentiation, Immunoglobulin Isotypes, Macrophages, Neutrophils, Plasma Cells, T-Lymphocytes, Viral Proteins, Mice, Knockout, Antigens, CD19, Integrases, STAT3 Transcription Factor, Mice
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