Activation of antiviral protein kinase leads to immunoglobulin E class switching in human B cells.
An epidemiologic association between viral infections and the onset of asthma and allergy has been documented. Also, evidence from animal and human studies has suggested an increase in antigen-specific immunoglobulin E (IgE) production during viral infections, and elevated levels of IgE are characteristic of human asthma and allergy. Here, we provide molecular evidence for the roles of viral infection and of activation of the antiviral protein kinase (PKR) (double-stranded-RNA [dsRNA]-activated protein kinase) in the induction of IgE class switching. The presence of dsRNA, a known component of viral infection and an activator of PKR, induced IgE class switching as detected by the expression of germ line epsilon in the human Ramos B-cell line. Furthermore, dsRNA treatment of Ramos cells resulted in the activation of PKR and in vivo activation of the NF-kappaB complex. Interestingly, infection of Ramos cells with rhinovirus (common cold virus) serotypes 14 and 16 resulted in the induction of germ line epsilon expression. To further evaluate the role of PKR in the viral induction of IgE class switching, we infected Ramos cells with two different vaccinia virus (cowpox virus) strains. Infection with wild-type vaccinia virus failed to induce germ line epsilon expression; however, a deletion mutant of vaccinia virus (VP1080) lacking the PKR-inhibitory polypeptide E3L induced the expression of germ line epsilon. Collectively, the results of our study define a common molecular mechanism underlying the role of viral infections in IgE class switching and subsequent induction of IgE-mediated disorders such as allergy and asthma.
Rager
K J
KJ
Asthma and Allergy Center, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224-6821, USA.
Langland
J O
JO
Jacobs
B L
BL
Proud
D
D
Marsh
D G
DG
Imani
F
F
D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000187:drug effects / Q000235:genetics*; D007073:Immunoglobulin E / Q000235:genetics* / Q000276:immunology; D009154:Mutation; D014407:Tumor Cells, Cultured; D014615:Vaccinia / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus; D019892:eIF-2 Kinase / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology
D007073:Immunoglobulin E; D019892:eIF-2 Kinase