title: B cell-derived circulating granzyme B is a feature of acute infectious mononucleosis.
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.
authors.affiliation: Cancer 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.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hagn
authors.affiliation: Centre for Immunotherapy and Vaccine Development, Queensland Institute of Medical Research , Brisbane, Queensland, Australia.
authors.forename: Archana
authors.initials: A
authors.lastname: Panikkar
authors.affiliation: Centre for Immunotherapy and Vaccine Development, Queensland Institute of Medical Research , Brisbane, Queensland, Australia.
authors.forename: Corey
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Laboratory Medicine and Pathology, Paediatrics and Microbiology, University of Minnesota Medical School , Minneapolis, Minnesota, USA.
authors.forename: Henry H
authors.initials: HH
authors.lastname: Balfour
authors.affiliation: Centre for Immunotherapy and Vaccine Development, Queensland Institute of Medical Research , Brisbane, Queensland, Australia.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Khanna
authors.affiliation: Cancer 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.
authors.forename: Ilia
authors.initials: I
authors.lastname: Voskoboinik
authors.affiliation: Cancer 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 ; Victorian Comprehensive Cancer Centre , Melbourne, Victoria, Australia.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Trapani