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Updated: Apr 6, 2026
A Colorimetric Assay that Specifically Measures Granzyme B Proteolytic Activity: Hydrolysis of Boc-Ala-Ala-Asp-S-Bzl
Published on: November 28, 2014
B cell-derived circulating granzyme B is a feature of acute infectious mononucleosis
Magdalena Hagn1, Archana Panikkar2, Corey Smith2
1Cancer Immunology Program, Cancer Cell Death Laboratory, Peter MacCallum Cancer Centre , East Melbourne, Victoria, Australia ; Sir Peter MacCallum Department of Oncology, The University of Melbourne , Parkvillie, Victoria, Australia.
Abstract:
Granzyme B (GzmB) is a serine protease best known for inducing target cell apoptosis when released by cytotoxic T lymphocytes (CTLs) or natural killer cells with pore-forming perforin. As a result, GzmB detected in the serum of virus-infected individuals has typically been attributed to these sources. Here, we show that patients with recently diagnosed infectious mononucleosis caused by Epstein-Barr virus (EBV) have high circulating levels of GzmB that may be derived from infected B cells early in course of disease. We recently reported that human B cells from healthy donors secrete active GzmB when stimulated in vitro through B-cell receptor (BCR) ligation and interleukin (IL)-21. We found that infecting B cells with EBV greatly amplified GzmB secretion in response to the same stimuli, but the expression was terminated once the infection had become latent. Our results represent a rare instance of GzmB expression by non-CTL/natural killer cells in the context of infection with a human pathogen.
Insights
Granzyme B (GzmB) is typically from immune cells, but this study finds it can be secreted by Epstein-Barr virus (EBV)-infected B cells during infectious mononucleosis. This suggests a new source for GzmB in viral infections.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Granzyme B (GzmB) is a serine protease primarily known for its role in apoptosis induction by cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells.
- Circulating GzmB in viral infections is usually attributed to CTLs or NK cells.
- The origin of GzmB in certain viral infections remains incompletely understood.
Purpose of the Study:
- To investigate the source of elevated Granzyme B (GzmB) levels in patients with infectious mononucleosis caused by Epstein-Barr virus (EBV).
- To determine if B cells, beyond the typical CTLs and NK cells, can secrete GzmB during EBV infection.
Main Methods:
- Analysis of GzmB levels in serum from patients with infectious mononucleosis.
- In vitro stimulation of human B cells from healthy donors via B-cell receptor (BCR) ligation and IL-21.
- Infection of B cells with EBV and assessment of GzmB secretion in response to stimuli during acute and latent phases.
Main Results:
- Patients with infectious mononucleosis exhibited high circulating GzmB levels.
- EBV infection significantly amplified GzmB secretion from B cells upon stimulation.
- GzmB secretion by B cells was observed during the acute phase of EBV infection but ceased upon latency establishment.
Conclusions:
- Infectious mononucleosis patients show elevated GzmB, potentially originating from EBV-infected B cells.
- This study identifies a novel source of GzmB secretion by non-CTL/NK cells in the context of a human viral pathogen.
- B cells can be a source of active GzmB during EBV infection, challenging the traditional view of GzmB origins.
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