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 rejectio...

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Bibliographic Details
Published in:Inflammation 2021-12, Vol.44 (6), p.2270-2278
Main Authors: Xu, Wen-Li, Wang, Ruo-lin, Liu, Zhe, Wu, Qiao, Li, Xian-Liang, He, Qiang, Zhu, Ji-Qiao
Format: Article
Language:English
Subjects:
Acute Disease
Adult
Aged
Alanine
Alanine transaminase
Antigens, CD19 - metabolism
B-Lymphocytes - drug effects
B-Lymphocytes - enzymology
B-Lymphocytes - immunology
Biomedical and Life Sciences
Biomedicine
Case-Control Studies
CD19 antigen
CD25 antigen
CD27 antigen
CD4 antigen
Cell Communication
Cell Proliferation
Cells, Cultured
Coculture Techniques
Feedback
Female
Flow cytometry
Glucocorticoids - therapeutic use
Graft rejection
Graft Rejection - diagnosis
Graft Rejection - drug therapy
Graft Rejection - enzymology
Graft Rejection - immunology
Granzyme B
Granzymes - metabolism
Helper cells
Hepatocytes
Humans
Immunoglobulin G
Immunoglobulin M
Immunology
Immunosuppressive Agents - therapeutic use
Interleukin-2 Receptor alpha Subunit - metabolism
Internal Medicine
Liver transplantation
Liver Transplantation - adverse effects
Liver transplants
Lymphocyte Activation - drug effects
Lymphocytes
Lymphocytes B
Lymphocytes T
Male
Middle Aged
Original Article
Pathology
Pharmacology/Toxicology
Rheumatology
Surface markers
T-Lymphocytes, Helper-Inducer - drug effects
T-Lymphocytes, Helper-Inducer - enzymology
T-Lymphocytes, Helper-Inducer - immunology
Tacrolimus
Up-Regulation
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Summary: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.
ISSN:0360-3997
1573-2576
DOI:10.1007/s10753-021-01498-9