Differential effects of tacrolimus versus sirolimus on the proliferation, activation and differentiation of human B cells

Opas Traitanon, James M. Mathew, Giovanna La Monica, Luting Xu, Valeria Mas, Lorenzo Gallon

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


The direct effect of immunosuppressive drugs calcineurin inhibitor (Tacrolimus, TAC) and mTOR inhibitor (Sirolimus, SRL) on B cell activation, differentiation and proliferation is not well documented. Purified human B cells from healthy volunteers were stimulated through the B Cell Receptor with Anti-IgM + anti-CD40 + IL21 in the absence / presence of TAC or SRL. A variety of parameters of B cell activity including activation, differentiation, cytokine productions and proliferation were monitored by flow cytometry. SRL at clinically relevant concentrations (6 ng/ml) profoundly inhibited CD19+ B cell proliferation compared to controls whereas TAC at similar concentrations had a minimal effect. CD27+ memory B cells were affected more by SRL than naïve CD27- B cells. SRL effectively blocked B cell differentiation into plasma cells (CD19+CD138+ and Blimp1+/Pax5low cells) even at low dose (2 ng/ml), and totally eliminated them at 6 ng/ml. SRL decreased absolute B cell counts, but the residual responding cells acquired an activated phenotype (CD25+/CD69+) and increased the expression of HLA-DR. SRL-treated stimulated B cells on a per cell basis were able to enhance the proliferation of allogeneic CD4+CD25- T cells and induce a shift toward the Th1 phenotype. Thus, SRL and TAC have different effects on B lymphocytes. These data may provide insights into the clinical use of these two agents in recipients of solid organ transplants.

Original languageEnglish (US)
Article numbere0129658
JournalPloS one
Issue number6
StatePublished - Jun 18 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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