ArticleJournal of immunology (Baltimore, Md. : 1950)2013
IL-21 and CD40L synergistically promote plasma cell differentiation through upregulation of Blimp-1 in human B cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 137 citations in OpenAlex.
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- Multiparametric Optimization of Human Primary B-Cell Cultures Using Design of Experiments.Scandinavian journal of immunology · 2025Article
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- Pro-Resolving Macrophage-Induced IL-35International journal of molecular sciences · 2025Article
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- TACI and endogenous APRIL in B cell maturation.Clinical immunology (Orlando, Fla.) · 2023Article
- B cell-intrinsic STAT3-mediated support of latency and interferon suppression during murine gammaherpesvirus 68 infection revealed through anbioRxiv : the preprint server for biology · 2023Article
- Tracking of activated cTfh cells following sequential influenza vaccinations reveals transcriptional profile of clonotypes driving a vaccine-induced immune response.Frontiers in immunology · 2023Article
- Termination of CD40L co-stimulation promotes human B cell differentiation into antibody-secreting cells.European journal of immunology · 2022Article
- Differential expression of circulating miRNAs after alemtuzumab induction therapy in lung transplantation.Scientific reports · 2022Article
- Optimized Protocols forFrontiers in immunology · 2022Article
- Cytogenetic Abnormalities in Multiple Myeloma: Incidence, Prognostic Significance, and Geographic Heterogeneity in Indian and Western Populations.Cytogenetic and genome research · 2022Article
- Oxygen level is a critical regulator of human B cell differentiation and IgG class switch recombination.Frontiers in immunology · 2022Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
After undergoing Ig somatic hypermutation and Ag selection, germinal center (GC) B cells terminally differentiate into either memory or plasma cells (PCs). It is known that the CD40L and IL-21/STAT3 signaling pathways play critical roles in this process, yet it is unclear how the B cell transcription program interprets and integrates these two types of T cell-derived signals. In this study, we characterized the role of STAT3 in the GC-associated PC differentiation using purified human tonsillar GC B cells and a GC B cell-like cell line. When primary GC B cells were cultured under PC differentiation condition, STAT3 inhibition by AG490 prevented the transition from GC centrocytes to preplasmablast, suggesting that STAT3 is required for the initiation of PC development. In a GC B cell-like human B cell line, although IL-21 alone can induce low-level Blimp-1 expression, maximum Blimp-1 upregulation and optimal PC differentiation required both IL-21 and CD40L. CD40L, although having no effect on Blimp-1 as a single agent, greatly augmented the amplitude and duration of IL-21-triggered Jak-STAT3 signaling. In the human PRDM1 locus, CD40L treatment enhanced the ability of STAT3 to upregulate Blimp-1 by removing BCL6, a potent inhibitor of Blimp-1 expression, from a shared BCL6/STAT3 site in intron 3. Thus, IL-21 and CD40L collaborate through at least two distinct mechanisms to synergistically promote Blimp-1 activation and PC differentiation.
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Registered trials
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