Abstract
Objectives: Increasing evidence has revealed the close correlation between immune cell functions and their intracellular metabolism. Mammalian target of rapamycin complex 1 (mTORC1) is the important metabolism-modulating signal that regulates cellular activities. In certain types of cell, it is known that mTORC1 activation depends on influx of l-leucine through an amino acid transporter, Slc7a5. In B cells, however, the expression and the role of Slc7a5 have never been investigated.
Methods: CD19+ B cells were obtained from peripheral blood of healthy adults and stimulated by a toll-like receptor 9 ligand, CpG oligodeoxynucleotides. The expression of Slc7a5 and l-leucine uptake were evaluated by RT-PCR, flow cytometry and radioisotope assay. Then the effect of Slc7a5 inhibition on mTORC1 activity, plasmablast differentiation and production of IgG and inflammatory cytokines were analyzed.
Results: CpG stimulation significantly induced the expression of Slc7a5 in B cells, resulting in l-leucine influx. Furthermore, inhibition of Slc7a5 abrogated mTORC1 activation, plasmablast differentiation, and production of IgG and inflammatory cytokines in CpG-stimulated B cells.
Conclusion: l-leucine influx through Slc7a5 critically regulates mTORC1 activity and the immunological responses of human B cells. Slc7a5-mTORC1 pathway may provide a novel therapeutic strategy for autoimmune diseases.
Acknowledgements
The authors thank the healthy volunteers for their cooperation and for consenting to participate in the study.
Conflict of interest
None.