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

• DOI: 10.1111/ajt.14013
• Publication Date: 2016-08-16T14:08:41Z
• Authors: H.A. Schlößer; M. Thelen; G. Dieplinger; A. von Bergwelt-B...; M. Garcia-Marquez; S. Reuter; A. Shimabukuro-Vo...; K. Wennhold; N. Haustein; D. Buchner; N. Heiermann; R. Kleinert; R. Wahba; V. Ditt; C. Kurschat; T. Cingöz; J. Becker; D.L. Stippel; M. von Bergwelt-B...
• Keywords: Adult; Graft Rejection; Male; 0301 basic medicine; Graft Survival; B-Lymphocyte Subsets; Prognosis; Kidney Transplantation; Transplant Recipients; ABO Blood-Group System; 3. Good health; 03 medical and health sciences; Postoperative Complications; Risk Factors; Blood Group Incompatibility; Living Donors; Humans; Kidney Failure, Chronic; Transplantation, Homologous; Female; Prospective Studies; Immunosuppressive Agents; Follow-Up Studies

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.