Dynamic analysis of B-cell subsets in de novo living related kidney transplantation with induction therapy of basiliximab

Abstract

Background: Accumulative evidence has suggested B-cell-mediated alloimmune response plays an important role in kidney transplantation. Monitoring the dynamics of B-cell subsets could enhance understanding of B-cell immunology in clinical transplantation, and may facilitate optimization of current immunosuppressive regimens.

Patients and methods: Between June 2011 and June 2012, 16 de novo living related kidney transplant recipients were enrolled in this study. All patients were given basiliximab as induction therapy. The maintenance therapy consisted of tacrolimus, mycophenolate mofetil (MMF), and steroids. Phenotype of B-cell subsets in peripheral blood was examined at day 0, day 1, day 3, day 7, day 14, month 1, month 3, and month 6.

Results: CD19(+) B cells in peripheral lymphocytes significantly increased by 1.8-2.1 times within 1 month after transplantation, and recovered to the baseline level at month 3. Notably in B cells, CD5(+)CD19(+)B cells dramatically decreased by 45% at month 6. CD19(+)CD27(+) memory B cells increased by 127% at month 6. B-cell activating factor receptor (BAFF-R) expression on the B-cell population was maintained at a high level of 91.7%-97.9%. Within 7 days after transplantation, Bm1 (IgD(+)CD38(-)) did not change apparently, Bm2 (IgD(+)CD38(int)) significantly increased, whereas Bm2' (IgD(+)CD38(high), germinal center founder cells), Bm3+Bm4 (IgD(-)CD38(high), germinal center B cells), early Bm5 (IgD(-)CD38(int)), and late Bm5 (IgD(-)CD38(-)) significantly decreased. After day 7, Bm1 stayed stable, Bm2 decreased to the baseline level (day 0), and Bm2' and Bm3+Bm4 kept decreasing, whereas early Bm5 and late Bm5 increased to baseline level. At month 6, Bm1 significantly increased, Bm2 was maintained at the baseline level, Bm2' constantly decreased to the lowest, and Bm3+Bm4 was slightly lower than the baseline, whereas early and late Bm5 increased to the baseline level.

Conclusions: The proportion of B cells in peripheral lymphocytes significantly increased at the early stage, whereas CD5(+)CD19(+)B cells consistently decreased after transplantation. Mature circulating B-cell subsets dynamically changed, especially at the early stage after transplantation, which might be attributed to the induction therapy.