Regulatory B Cells in Organ Transplantation: A Review of Their Role and Potential Therapeutic Applications

This paper systematically reviews the potential role of regulatory B cells (Bregs) in solid organ transplantation, revealing their promising functions in inducing immune tolerance and predicting transplant rejection risks, providing theoretical support for future Breg cell-based immunomodulatory therapies.

 

Literature Overview

This article, titled 'Regulatory B Cells in Organ Transplantation: A Review of Their Role and Potential Therapeutic Applications', published in the journal Antibodies, reviews and summarizes the immunomodulatory functions of regulatory B cells in solid organ transplantation and their relationships with transplant tolerance and rejection. The paper provides a detailed analysis of changes in different B cell subsets before and after transplantation, as well as their associations with donor-specific antibodies (DSAs) and immunosuppressive functions. It further discusses the roles of Bregs in other diseases such as autoimmune disorders, infections, and cancers, highlighting their importance in maintaining immune homeostasis.

Background Knowledge

Regulatory B cells (Bregs) are a subset of B cells with immunosuppressive functions, primarily modulating T cells, macrophages, and dendritic cells through the secretion of cytokines such as IL-10 and TGF-β. In the field of organ transplantation, Bregs are believed to play a critical role in suppressing excessive immune responses and promoting graft tolerance. Although studies in mouse models have confirmed the role of Bregs in transplant tolerance, their exact mechanisms in humans remain controversial. Conventional immunosuppressive therapies, such as anti-CD20 treatment, effectively reduce B cell numbers but may also diminish Breg-mediated tolerance, thereby increasing the risk of acute or chronic rejection. Additionally, Bregs are influenced by the gut microbiota and metabolites (e.g., butyrate) as well as neurotransmitters (e.g., GABA), further impacting immune homeostasis. Therefore, understanding Breg function in transplantation can facilitate the development of novel tolerance-inducing strategies and personalized immune monitoring protocols.

 

 

Research Methods and Experiments

This study employs a literature review approach to systematically analyze the roles of regulatory B cells in solid organ transplantation, including their phenotypic characteristics, differentiation mechanisms, immunomodulatory functions, and changes observed during rejection episodes. Researchers used flow cytometry to define phenotypes of different B cell subsets, such as CD19+CD24hiCD38hi (transitional B cells), CD19+CD24hiCD27+ (memory B cells), and CD19+CD24hiCD27intCD138hi (plasmablasts). Additionally, the study assessed Breg distribution across different transplant recipients (kidney, liver, heart, lung) and their correlation with transplant outcomes (e.g., acute or chronic rejection, graft survival, tolerance). Some studies employed cluster analysis to explore associations between overall B cell subset phenotypes and transplant risks, rather than focusing solely on individual subsets.

Key Conclusions and Perspectives

• Regulatory B cells (Bregs) play a crucial immunomodulatory role in organ transplantation, primarily through the secretion of immunosuppressive cytokines such as IL-10, TGF-β, and GrB, which suppress inflammatory responses from T cells and macrophages
• In kidney transplant recipients, transitional B cells (CD19+CD24hiCD38hi) and plasmablast Breg subsets are associated with reduced rejection risk during the early post-transplant period
• B cell depletion therapy induced by anti-CD20 may simultaneously reduce Breg populations, increasing the risk of acute rejection and chronic allograft vasculopathy
• In liver transplant recipients, memory Bregs are decreased during acute rejection episodes, while transitional Bregs expand during immunosuppressive regimen switches (e.g., tacrolimus to sirolimus), suggesting their potential role in tolerance induction
• In heart and lung transplant models, adoptive transfer of Bregs prolongs graft survival and enhances Treg expansion, indicating their potential in xenotransplantation tolerance
• The study also notes that Breg definitions remain inconsistent; different subsets (e.g., B10, BR1, CD5+CD1d+) possess diverse functions and phenotypes, and their roles may depend on the local microenvironment and intercellular signaling networks

Research Significance and Prospects

Regulatory B cells demonstrate potential as novel biomarkers and therapeutic targets in transplant immunology. Future research should focus on clarifying Breg subset phenotypes, functional heterogeneity, and dynamic changes across different transplant types. Moreover, strategies to stabilize or expand Bregs through microbiota modulation, metabolites (e.g., butyrate), or immunotherapeutic interventions (e.g., IL-21 inhibition, GITRL, PD-L1 agonists) represent critical directions for inducing transplant tolerance. The study also supports the integration of Breg-based immune risk stratification systems into clinical practice to optimize personalized immunosuppressive therapy and reduce long-term post-transplant complications.

 

 

Conclusion

The roles of regulatory B cells (Bregs) in organ transplantation are gradually being elucidated. They not only exert immunosuppressive functions in autoimmune and inflammatory diseases but also demonstrate key immunomodulatory capacities in transplant tolerance. Despite existing evidence linking Bregs to transplant rejection and tolerance, further mechanistic studies are required, particularly regarding their phenotypic and functional stability in humans, as well as their interaction networks with other immune cells. In the future, Breg monitoring and modulation may become integral components of transplant immunology, offering novel strategies for personalized immunotherapy and tolerance induction. Additionally, developing immunotherapeutic protocols capable of stabilizing or expanding Bregs—such as cytokine regulation, microbiota intervention, or PD-L1 modulation—could improve long-term graft survival and reduce the side effects of immunosuppressive agents.

 

Marina Fernández-González, Santiago Llorente, José Antonio Galián, Isabel Legaz, and Manuel Muro. Influence and Role of Regulatory B Cells in Organ Transplantation: The State of the Art, Prospects, and Emerging Insights. Antibodies.