Prospective Analyses of Circulating B Cell Subsets in ABO-Compatible and ABO-Incompatible Kidney Transplant Recipients

Immunosuppressive strategies applied in renal transplantation traditionally focus on T-cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B-cell functions has only recently entered the field of transplantation. Similar to T cells distinct B-cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B-cell subsets in peripheral blood of AB0-compatible (n=27) and AB0-incompatible (n=10) renal transplant recipients. Activated B cells were transiently and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in AB0-incompatible patients resulted in long-lasting B-cell depletion and in a naive phenotype of repopulating B cells one year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B-cell subsets. Taken together, our study demonstrates remarkable effects of standard immunosuppression on circulating B-cell subsets. Furthermore the B-cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B-cell subsets could be of clinical benefit in renal transplantation. This article is protected by copyright. All rights reserved.