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

Abstract

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 the peripheral blood of AB0-compatible (n = 27) and AB0-incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased 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 naïve phenotype of repopulating B cells 1 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. Our study demonstrates the 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.

T cell reconstitution after lymphocyte depletion features a different pattern of inhibitory receptor expression in ABO- versus HLA-incompatible kidney transplant recipients

“…We also found a higher rate of CD25 high CD127 low CD4 + T regs after ABOi compared with HLAi recipients. This point is in line with previous studies that described similar CD4 + T reg rates after ABO-compatible or -incompatible kidney transplantation [52], whereas lower rates of T regs were associated with chronic rejection (a clinical setting frequently associated with HLAi transplantation) [53,54].There are several important limitations to the conclusions of our study. First, we analyzed a limited number of patients, which could blur important differences and/or correlations between groups, owing to the large variability observed for many important parameters.…”

Belimumab in kidney transplantation: an experimental medicine, randomised, placebo-controlled phase 2 trial

“…Similarly, patients with a higher B cell IL-10:TNF ratio have a slower decline in transplant function and reduced allograft loss 17,18 . In contrast, patients with rejection following ABO incompatible transplantation had fewer CD24 high /CD27 + memory B cells 19 . Together, these data show that B cells can play both a positive and negative role in transplantation and highlight the need to identify immunosuppressants that preserve the immunoregulatory aspect of B cell function.…”

Effector and regulatory B cells in immune-mediated kidney disease

“…For example, different agents used as induction therapy result in different proportions of Bregs. Induction with alemtuzumab (a depleting monoclonal antibody directed against CD52, which is present on many leukocyte populations including B cells) augmented naïve, immature and CD5 + CD1d hi B cell numbers following repopulation, to a greater extent than did basiliximab (an anti-CD25 antagonist), and the alemtuzumab-treated patients had improved graft outcomes and lower levels of DSAs(102).In ABO-incompatible renal transplant recipients, treatment with rituximab resulted in a predominantly naïve B cell phenotype upon B cell repopulation (containing a greater proportion of IL-10-producing Breg cells) 1 year following transplantation(100). In contrast, another study reported increased rates of acute transplant rejection following rituximab induction therapy(103), possibly due to depletion of Breg cells, which express CD20, but this finding has not been universal in other rituximab studies(104,105).…”