NIV Congres

In organ transplantation, the composition of the peripheral B cell compartment is increasingly identified as an important determinant for graft outcome. Whereas naïve and transitional B cells have been associated with long-term allograft survival and operational tolerance, memory B cells have been linked to decreased allograft survival. We studied the peripheral B cell phenotype of kidney transplant recipients before transplantation, at discharge and at time of rejection using flow cytometry. Furthermore, isolated CD19⁺ B cells were polyclonally activated and analysed for their immunoglobulin production capacity by ELISPOT assays. The study was performed in 21 patients who experienced an acute rejection episode within the first 6 months after transplantation and 22 patients without acute rejection in our study.

Flow cytometric analysis of memory and naïve B cell subsets, classified according to IgD and CD27 staining, revealed a significant decrease in peripheral memory B cells at time of acute rejection (p<0.0001). In contrast, in patients without acute rejection, the B cell phenotype remained stable in time. The results of these phenotypic analyses were confirmed by functional data. When peripheral B cells were analysed for their capacity to produce immunoglobulins, we observed an increase in the ratio of IgM/IgG producing B cells upon acute rejection (p=0.0003). Coinciding with this phenotypic and functional shift towards naïve B cells at time of acute rejection we observed a strong decrease in peripheral B cells bearing the homing receptor CXCR5 (p=0.0004), which was not observed in patients without rejection. This suggests that the change in B cell composition may be due to homing of memory B cells towards lymphoid organs or the graft. The latter is supported by our findings in a separate patient cohort (n=89) showing that during acute rejection mRNA expression of CD20 and the chemoattractant CXCL13 (ligand for CXCR5) in kidney biopsies is significantly elevated (p=0.047 and p=0.004, respectively).

In conclusion, our data suggest that memory B cells may be involved in acute cellular kidney allograft rejection. These observations warrant more research into the exact phenotype of the graft infiltrating B cells during acute rejection and their possible interaction with T cells.