Human B Cells Secrete Granzyme B When Recognizing Viral Antigens in the Context of the Acute Phase Cytokine IL-21

• Published in: The Journal of immunology (1950) Vol. 183; no. 3; pp. 1838 - 1845
• Main Authors: Hagn, Magdalena, Schwesinger, Elisabeth, Ebel, Verena, Sontheimer, Kai, Maier, Julia, Beyer, Thamara, Syrovets, Tatiana, Laumonnier, Yves, Fabricius, Dorit, Simmet, Thomas, Jahrsdorfer, Bernd
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.08.2009
• Subjects: Acute-Phase Proteins; Antigens, Viral - immunology; B-Lymphocytes - immunology; B-Lymphocytes - secretion; Endosomes - virology; Granzymes - secretion; Humans; Immunity; Immunophenotyping; Interleukins - immunology; Signal Transduction; Vaccination; Virus Internalization
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.0901066

Human B cells are currently not known to produce the proapoptotic protease granzyme B (GrB) in physiological settings. We have discovered that BCR stimulation with either viral Ags or activating Abs in the context of the acute phase cytokine IL-21 can induce the secretion of substantial amounts of GrB by human B cells. Importantly, GrB response to viral Ags was significantly stronger in B cells from subjects recently vaccinated against the corresponding viruses as compared with unvaccinated subjects. GrB-secreting B cells featured a homogeneous CD19+CD20+CD27−CD38−IgD− phenotype, improved survival, and enhanced expression of costimulatory, Ag-presenting and cell-adhesion molecules. B cell-derived GrB was enzymatically active and its induction required the activation of similar signaling pathways as those in CTLs. Our findings suggest that GrB-secreting B cells support the early antiviral immune response against viruses with endosomal entry pathways, thereby counteracting overwhelming viral replication at the beginning of an infection until virus-specific T cells from draining lymph nodes arrive at the site of infection. Our data may also explain the elevated serum GrB levels found in the early phase of various viral diseases.