Human B cells secrete granzyme B when recognizing viral antigens in the context of the acute phase cytokine IL-21.
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.
Hagn
Magdalena
M
Laboratory of Tumor and B Cell Immunology, Institute of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, 89081 Ulm, Germany.
Schwesinger
Elisabeth
E
Ebel
Verena
V
Sontheimer
Kai
K
Maier
Julia
J
Beyer
Thamara
T
Syrovets
Tatiana
T
Laumonnier
Yves
Y
Fabricius
Dorit
D
Simmet
Thomas
T
Jahrsdörfer
Bernd
B
D000209:Acute-Phase Proteins; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D011992:Endosomes / Q000821:virology; D053804:Granzymes / Q000378:metabolism*; D006801:Humans; D007109:Immunity; D016130:Immunophenotyping; D007378:Interleukins / Q000276:immunology*; D015398:Signal Transduction; D014611:Vaccination; D053586:Virus Internalization; D000098546:Interleukin-21
D000209:Acute-Phase Proteins; D000956:Antigens, Viral; D007378:Interleukins; D053804:Granzymes; D000098546:Interleukin-21