ArticleThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation2021
IRF4 ablation in B cells abrogates allogeneic B cell responses and prevents chronic transplant rejection.
Article in The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- IL-6/IL-6R Signaling Blockade Alleviates Chronic Allograft Rejection by Modulating Germinal Center B Cells and Allograft Inflammation in Murine Cardiac Transplantation.Journal of inflammation research · 2025Article
- CD4Nature immunology · 2024Article
- An agent-based model of cardiac allograft vasculopathy: toward a better understanding of chronic rejection dynamics.Frontiers in bioengineering and biotechnology · 2023Article
- Continuous Expression of Interferon Regulatory Factor 4 Sustains CD8Research (Washington, D.C.) · 2023Article
- B-cell response in solid organ transplantation.Frontiers in immunology · 2022Review
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8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgoundB cells contribute to chronic transplant rejection by producing donor-specific antibodies and promoting T cell response, but how these processes are regulated at the transcriptional level remains unclear. Herein, we investigate the role of transcription factor interferon regulatory factor 4 (IRF4) in controlling B cell response during chronic transplant rejection.
methodsWe generated the Irf4
resultsIRF4 is dynamically expressed at different stages of B cell development and is absent in germinal center (GC) B cells. However, IRF4 ablation in the B cell lineage primarily eliminates GC B cells in both naïve and NP-KLH immunized mice. In the transplantation setting, IRF4 functions intrinsically in B cells and governs allogeneic B cell responses at multiple levels, including GC B cell generation, plasma cell differentiation, donor-specific antibody production, and support of T cell response. B cell-specific IRF4 deletion combined with transient CTLA4-Ig treatment abrogates acute and chronic cardiac allograft rejection in naïve recipient mice but not in donor skin-sensitized recipients.
conclusionsB cells require IRF4 to mediate chronic transplant rejection. IRF4 ablation in B cells abrogates allogeneic B cell responses and may also inhibit the ability of B cells to prime allogenic T cells. Targeting IRF4 in B cells represents a potential therapeutic strategy for eliminating chronic transplant rejection.
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