Regulatory B Cells And Renal Transplantation Immune Status Relationship And Mechanism Research

Objectives:To investigate the dynamic alteration of B cell activating factor (BAFF) in kidney transplantation recipients, we compared its level in the set-ting of induced donor specific tolerance by combined kidney and hem-atopoietic stem cell (HSC) transplantation., and we further evaluated the distinct function and subpopulations of B cells with regulatory po-tential in recipients with different posttransplant immune status or im-munosuppressive regimens so as to preliminarily clarify the effect and its mechanism of B cells on the establishment and maintenance of kid-ney transplant tolerance.Methods:Along with conventional deceased donor and living donor kidney trans-plantation, we conducted combined kidney and HSC transplantation on eligible recipients in order to induce donor specific immune tolerance. The recipients were divided into5groups, defined as those who re-ceived combined transplantation (TOL), those who received conven-tional surgery while remained stable allograft function (STA), those who suffered from acute rejection (AR) or chronic allograft nephropa-thy (CR), and those who was attacked by infection (INF). Healthy in-dividuals were also enrolled as control (HC). We observed the dynamic alteration of BAFF level at different time points in TOL recipients, and analyzed its distinction among recipients with different immune condi-tions. We also studied candidates of Breg and their competence in IL-10production so as to elucidate the effects and the mechanisms of B cell activation, reconstitution, and Bregs on the establishment and maintenance of immune tolerance. We then assessed the impact on Bregs of STA recipients who were maintained on various immunosup-pressant so that we might illuminate the underlying factors that may in-fluence their peripheral Bregs.Results:BAFF level was higher in TOL recipients than that in recipients per-formed by conventional surgery, and could persist for1year after trans-plantation. The frequency of total B cells was higher in TOL recipients and healthy volunteers compared with AR, CR, and STA recipients. Par- ticularly, we observed increased frequency of CD19+CD24hiCD38hi and CD19+CD24hiCD27+B cells in these two groups. Regarding to the func-tion of B cells in the two groups, IL-10+B cells were also prevailed. Notably, although TOL and healthy volunteers displayed a higher fre-quency of CD19+CD24hiCD38hiIL-10+and CD19+CD24hiCD27+IL-10+B cells, it could still not specify the phenotype of IL-10producing B cells due to its small proportion in the above2subsets. We also found a higher frequency of CD19+CD24hiCD38hi and CD19+CD24hiCD27+B cells in recipients who were on rapamycin-based immunosuppresive regimen compared with whom received CNI-based one.Conclusion:The clinical investigation revealed the potential immune regulatory effects of B cells after kidney transplantation and implied that the prolif-eration and survival of B cells might participate in the establishment of immune tolerance after combined HSC and kidney transplantation. Var-ious B cell subpopulations including CD19+CD24hiCD38hi and CD19+CD24hiCD27+B cells may be closely associated with the mainte-nance of immune tolerance, and regarded as candidates of Breg pheno-types. Although heterogeneity was seen in Breg, IL-10may be the key cytokine that involved in immune regulation and establishment of trans-plant tolerance by Bregs. We also showed that rapamycin, as a promising tolerance-inducing immunosuppressant, may increase the frequency of Breg subpopulations and impetus the establishment of immune tolerance by altering B cell function.