Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals
Open accessAbstract
Recent results suggest that plasma cell longevity is not an intrinsic capacity, but depends on yet unknown factors produced in their environment. In this study, we show that the cytokines IL-5, IL-6, TNF-α, and stromal cell-derived factor-1α as well as signaling via CD44 support the survival of isolated bone marrow plasma cells. The cytokines IL-7 and stem cell factor, crucially important for early B cell development, do not mediate plasma cell survival, indicating that plasma cells and early B cells have different survival requirements. As shown in IL-6-deficient mice, IL-6 is required for a normal induction, but not for the maintenance of plasma cell responses in vivo, indicating that the effects of individual survival factors are redundant. Optimal survival of isolated plasma cells requires stimulation by a combination of factors acting synergistically. These results strongly support the concept that plasma cell survival depends on niches in which a combination of specific signals, including IL-5, IL-6, stromal cell-derived factor-1α, TNF-α, and ligands for CD44, provides an environment required to mediate plasma cell longevity.
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IL-6 promotes antibody production by directly acting on plasma cells and by indirectly promoting Bcl6-dependent follicular CD4+ T (Tfh) cell differentiation together with IL-21.
“Indeed, IL-6 promotes antibody production by directly acting on plasma cells and by indirectly promoting Bcl6-dependent follicular CD4(+) T (Tfh) cell differentiation together with IL-21 (Fig. 2) (143–146).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [145]
The Discussion and Figure 4 describe IL-6 acting directly on isolated plasma cells to support their survival and antibody-secreting function in culture. The paper does not address IL-21 or Bcl6-dependent Tfh differentiation, so it does not support the indirect pathway in the citing sentence. It also reports that IL-6 was not essential for maintaining antibody titers in vivo. (LLM, conf=0.88)
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Self-citation
- Authors
- Cassese, G., Arce, S., Hauser, A. E., Lehnert, K., Moewes, B., Mostarac, M., Muehlinghaus, G., Szyska, M., Radbruch, A., & Manz, R. A.
- Affiliations
- German Rheumatism Research Centre (DE)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-08
- Volume
- 171
- Issue
- 4
- Pages
- 1684-1690
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2128395962
- Cited by
- 487
- References
- 1
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 18 · 2023: 21 · 2022: 21 · 2021: 26 · 2020: 25 · 2019: 28 · 2018: 23 · 2017: 15 · 2016: 18 · 2015: 21 · 2014: 21 · 2013: 24 · 2012: 23
- FWCI
- 7.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- plasma cell survival, interleukin-6, IL-5, TNF-α, stromal cell-derived factor-1α, CD44 signaling, cytokine synergy, bone marrow plasma cells, IL-7, stem cell factor, IL-6-deficient mice
- MeSH terms
- Animals, Antibodies, Monoclonal, Antibody Formation, Bone Marrow Cells, Cell Adhesion, Cell Separation, Cell Survival, Cells, Cultured, Drug Synergism, Gene Expression Regulation, Mice, Inbred BALB C, Mice, Inbred C57BL, Plasma Cells, Signal Transduction, Interleukin-5, Interleukin-6, Cytokines, Apoptosis, Mice, Knockout, Lymphocyte Count, Mice
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