Introduction

Elevated frequencies of transitional B cells have been reported in patients tolerant of renal allografts, as defined by stable graft function after withdrawal of immunosuppression for more than 1 year. Transitional B cells display an immature phenotype and can produce anti-inflammatory cytokine IL-10 secretion upon activation. Whether this is a biomarker of tolerance or a result of immunosuppressive drug therapy is unclear. To test this, we measured the frequencies of different B cell subsets, including transitional B cells, in the peripheral blood of cynomolgus macaques treated with standard Tacrolimus-based immunosuppression but not transplanted.

Methods

Four healthy monkeys were treated with standard maintenance immunosuppression containing Tacrolimus (0.1 mg/kg), Mycophenolate mofetil (200mg), and methylprednisolone (40mg tapered to 1mg over 2 weeks) daily for 150 days. PBMCs were stained with the following antibodies: CD3, CD20, CD38, CD27, IgD, IgM, CD8, and eFluor viability dies and their phenotype analyzed using a FACSVerse flow cytometer.

Results

Three animals underwent the full 150 days treatment course. One animal (M5416) required a short immunosuppression holiday due to weight loss. After one month, we observed a dramatic decrease in the frequency of CD38^hiCD27^–IgD⁺ transitional peripheral blood B cells (<10% of baseline values). Levels remained low for the duration of treatment. Interestingly, transitional B cells in M5416 returned to normal values after immunosuppression was stopped and decreased again when treatment was resumed, further confirming the effect of the drug therapy. In contrast, the frequencies of CD27⁺ memory B cells were increased.

Conclusion

Conventional, triple-drug immunosuppression leads to a near complete absence of transitional B cells in the peripheral blood of NHPs. It is not clear whether this is due to their depletion or their maturation into effector or memory B cells. These data will shed light on whether the level of transitional B cells represent a biomarker for tolerance in renal allograft recipients.

CITATION INFORMATION: Paster J., Pruner K., Hanekamp M., O. J., Sommer W., Robins K., Bean A., Benichou G., Madsen J. Tacrolimus-Based Maintenance Immunosuppression Decreases the Number of Peripheral Blood Transitional B Cells in Nonhuman Primates Am J Transplant. 2017;17 (suppl 3).

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