Granzyme B–Producing B Cells Function as a Feedback Loop for T Helper Cells in Liver Transplant Recipients with Acute Rejection

Granzyme B–producing B cells have been reportedly reported to be an important regulatory B cell subset in the pathogenesis of many diseases. However, its role in liver transplant recipients with acute rejection has never been well elucidated. Seventeen liver transplant recipients with acute rejection and 25 controls with stable liver function were enrolled in this study to determine the function of granzyme B–producing B cells via flow cytometry. Liver transplant recipients with acute rejection had higher expression of granzyme B in CD19⁺B cells when compared with controls. Following rejection, the granzyme B production was even elevated although comparison failed to reach significance. The percentages of CD27⁺granzyme B⁺CD19⁺B cells and CD138⁺granzyme B⁺CD19⁺B cells were lower than those of CD27⁻granzyme B⁺CD19⁺B cells and CD138⁻granzyme B⁺CD19⁺B cells in patients with acute rejection, respectively. While the production of CD27 and CD138 was not different between liver transplant recipients with and without acute rejection but increased expression of the two surface markers was observed following rejection. Furthermore, the frequency of granzyme B⁺CD19⁺B cells correlated with the level of alanine aminotransferase instead of tacrolimus. CD19⁺B cells could produce granzyme B when stimulated with IgG + IgM and CpG in the presence of the supernatant of activated CD4⁺CD25⁻T cells. In return, granzyme B⁺CD19⁺B cells could suppress the proliferation of CD4⁺CD25⁻T cells in a granzyme B– and contact-dependent manner. The increased expression of granzyme B in CD19⁺B cells from liver transplant recipients with acute rejection might function as a feedback loop for the activation of the CD4⁺CD25⁻T cells.