Dynamic changes of B‐cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection

B cells play an important role in the immune responses which affect the outcomes of kidney allografts. Dynamic changes of B‐cell compartments in clinical kidney transplantation are still poorly understood. B‐cell subsets were prospectively monitored using flow cytometry for 1 year in 98 kidney transplant recipients. Data were correlated with immunosuppression and clinical outcomes. An increase in the total population of B lymphocytes was observed during the first week after transplantation. The level of IgMhighCD38highCD24high transitional B cells reduced significantly up until the third month, with partial repopulation in the first year. Lower numbers of transitional B cells in the third month were associated with higher risk of graft rejection. IgM+IgD+CD27− naive B cells did not change within follow‐up. IgM+CD27+ nonswitched memory B cells and IgM−CD27+ switched memory B cells increased on post‐operative day 7. IgM−CD38highCD27high plasmablasts showed similar kinetics during the first post‐transplant year, similar to transitional B cells. In conclusion, sensitized kidney transplant recipients as well as those with either acute or chronic rejection within the first post‐transplant year exhibited lower levels of transitional B cells. Therefore, these data further support the hypothesis that transitional B cells have a protective role in kidney transplantation.

[1]  M. Hudson.  Human , 2018, Critical Theory and the Classical World.

[2]  B. Lambrecht,et al.  Calcineurin inhibitors dampen humoral immunity by acting directly on naive B cells , 2015, Clinical and experimental immunology.

[3]  R. Borrows,et al.  Transitional B Lymphocytes Are Associated With Protection From Kidney Allograft Rejection: A Prospective Study , 2015, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[4]  J. D. de Fijter,et al.  B Cell Markers of Operational Tolerance Can Discriminate Acute Kidney Allograft Rejection From Stable Graft Function , 2015, Transplantation.

[5]  O. Viklicky,et al.  Circulating biomarkers of tolerance. , 2015, Transplantation reviews.

[6]  D. Laplaud,et al.  Tolerant Kidney Transplant Patients Produce B Cells with Regulatory Properties. , 2015, Journal of the American Society of Nephrology : JASN.

[7]  H. Koenen,et al.  Longitudinal Analysis of T and B Cell Phenotype and Function in Renal Transplant Recipients with or without Rituximab Induction Therapy , 2014, PloS one.

[8]  Ji Hyun Yu,et al.  Decrease of immature B cell and interleukin-10 during early-post-transplant period in renal transplant recipients under tacrolimus based immunosuppression. , 2014, Transplant immunology.

[9]  L. Dongwei,et al.  Dynamic analysis of B-cell subsets in de novo living related kidney transplantation with induction therapy of basiliximab. , 2014, Transplantation proceedings.

[10]  J. Pers,et al.  B cells display an abnormal distribution and an impaired suppressive function in patients with chronic antibody-mediated rejection. , 2014, Kidney international.

[11]  V. Lánská,et al.  CD14+CD16+ and CD14+CD163+ monocyte subpopulations in kidney allograft transplantation , 2014, BMC Immunology.

[12]  D. Rush,et al.  Banff 2013 Meeting Report: Inclusion of C4d‐Negative Antibody‐Mediated Rejection and Antibody‐Associated Arterial Lesions , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[13]  J. Pers,et al.  Regulatory B Cells: An Exciting Target for Future Therapeutics in Transplantation , 2014, Front. Immunol..

[14]  K. Tarte,et al.  Unique B Cell Differentiation Profile in Tolerant Kidney Transplant Patients , 2014, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[15]  N. Perico,et al.  In Kidney Transplant Patients, Alemtuzumab but Not Basiliximab/Low-Dose Rabbit Anti-Thymocyte Globulin Induces B Cell Depletion and Regeneration, Which Associates with a High Incidence of De Novo Donor-Specific Anti-HLA Antibody Development , 2013, The Journal of Immunology.

[16]  H. Volk,et al.  B-Cell-Related Biomarkers of Tolerance are Up-Regulated in Rejection-Free Kidney Transplant Recipients , 2013, Transplantation.

[17]  F. Barbé-Tuana,et al.  Preserving the B-Cell Compartment Favors Operational Tolerance in Human Renal Transplantation , 2012, Molecular medicine.

[18]  P. Friend,et al.  B Cell Repopulation After Alemtuzumab Induction—Transient Increase in Transitional B Cells and Long-Term Dominance of Naïve B Cells , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[19]  O. Viklicky,et al.  Regulatory T cells in kidney transplant recipients: the effect of induction immunosuppression therapy. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[20]  I. T. Ten Berge,et al.  Circulating lymphocyte subsets in different clinical situations after renal transplantation , 2012, Immunology.

[21]  V. Seyfert-Margolis,et al.  Donor‐Specific Indirect Pathway Analysis Reveals a B‐Cell‐Independent Signature which Reflects Outcomes in Kidney Transplant Recipients , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[22]  L. Boon,et al.  In Vitro Effects of Rituximab on the Proliferation, Activation and Differentiation of Human B Cells , 2012, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[23]  Patricia A. Lovelace,et al.  Phenotypic Evaluation of B-Cell Subsets After Rituximab for Treatment of Acute Renal Allograft Rejection in Pediatric Recipients , 2011, Transplantation.

[24]  E. S. St. Clair,et al.  Characterization of a rare IL-10-competent B-cell subset in humans that parallels mouse regulatory B10 cells. , 2011, Blood.

[25]  M. Stegall,et al.  The (re)emergence of B cells in organ transplantation , 2010, Current opinion in organ transplantation.

[26]  Graham M Lord,et al.  Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. , 2010, The Journal of clinical investigation.

[27]  M. Suthanthiran,et al.  Identification of a B cell signature associated with renal transplant tolerance in humans. , 2010, The Journal of clinical investigation.

[28]  D. Isenberg,et al.  CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. , 2010, Immunity.

[29]  E. Thervet,et al.  Outcome of Subclinical Antibody‐Mediated Rejection in Kidney Transplant Recipients with Preformed Donor‐Specific Antibodies , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[30]  P. Reinke,et al.  Anti-Human Leukocyte Antigen and Donor-Specific Antibodies Detected by Luminex Posttransplant Serve as Biomarkers for Chronic Rejection of Renal Allografts , 2009, Transplantation.

[31]  M. Stegall,et al.  Mechanisms of Alloantibody Production in Sensitized Renal Allograft Recipients , 2009, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[32]  A. Ho,et al.  Induction of CD4+ T-cell anergy and apoptosis by activated human B cells. , 2008, Blood.

[33]  S. Knechtle,et al.  Calcineurin Inhibitor Withdrawal After Renal Transplantation with Alemtuzumab: Clinical Outcomes and Effect on T‐Regulatory Cells , 2008, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[34]  M. Mohty,et al.  Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond , 2007, Leukemia.

[35]  M. Bokarewa,et al.  Phenotypic and functional characterization of human CD25+ B cells , 2006, Immunology.

[36]  A. Bhan,et al.  A Case for Regulatory B Cells1 , 2006, The Journal of Immunology.

[37]  M. Zand,et al.  Polyclonal Rabbit Antithymocyte Globulin Triggers B-Cell and Plasma Cell Apoptosis by Multiple Pathways , 2005, Transplantation.

[38]  L. Staudt,et al.  Human blood IgM "memory" B cells are circulating splenic marginal zone B cells harboring a prediversified immunoglobulin repertoire. , 2004, Blood.

[39]  P. Dyer,et al.  Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome1 , 2003, Transplantation.

[40]  D. San Segundo,et al.  Frequencies of circulating B-cell subpopulations before kidney transplantation identify patients at risk of acute rejection. , 2015, Transplantation proceedings.