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 journalArticle

16 Citations (Scopus)

Abstract

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
Volume10
Issue number6
DOIs
StatePublished - Jun 18 2015
Externally publishedYes

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tacrolimus
Tacrolimus
Sirolimus
B-lymphocytes
B-Lymphocytes
Chemical activation
Cells
Cell Differentiation
Transplants
Cell Proliferation
T-cells
Lymphocytes
Flow cytometry
Cell proliferation
organ transplantation
Phenotype
HLA-DR Antigens
phenotype
immunosuppressive agents
Immunosuppressive Agents

All Science Journal Classification (ASJC) codes

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

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Differential effects of tacrolimus versus sirolimus on the proliferation, activation and differentiation of human B cells. / Traitanon, Opas; Mathew, James M.; Monica, Giovanna La; Xu, Luting; Mas, Valeria; Gallon, Lorenzo.

In: PLoS ONE, Vol. 10, No. 6, e0129658, 18.06.2015.

Research output: Contribution to journalArticle

Traitanon, Opas ; Mathew, James M. ; Monica, Giovanna La ; Xu, Luting ; Mas, Valeria ; Gallon, Lorenzo. / Differential effects of tacrolimus versus sirolimus on the proliferation, activation and differentiation of human B cells. In: PLoS ONE. 2015 ; Vol. 10, No. 6.
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