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Anti RSV immunoglobulin isotype selection requires dsRNA‐activated protein kinase (PKR)
Author(s) -
Minor Radiah Ann Corn,
Croom Brittany,
Imani Farhad
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.861.11
Subject(s) - protein kinase r , isotype , antibody , immune system , biology , virology , eif 2 kinase , virus , western blot , protein kinase a , microbiology and biotechnology , immunology , kinase , gene , mitogen activated protein kinase kinase , monoclonal antibody , biochemistry , cyclin dependent kinase 2
Respiratory syncytial virus (RSV) is the most common cause of severe respiratory tract infections in infants and young children world wide. A great deal of research has been focused on understanding the immune response to RSV in hopes of developing a safe and effective vaccine. Previous experiments by our lab showed that the double‐stranded RNA‐activated protein kinase (PKR) was required for RSV and dsRNA induction of inflammation. In the present study, we have focused on the role of PKR in adaptive immunity. Wild‐type and PKR‐deficient mice were infected with RSV (2 × 10 7 pfu/mouse) and after 1, 7 and 14 days, the levels of serum immunoglobulins were determined. Our data showed that over time, the total levels of IgG 2A and IgG 1 within the serum of WT but not PKR‐deleted mice increased. Furthermore, western blot analysis on extracts from RSV infected cells, showed that serum from infected WT mice contained significantly greater levels of RSV reactive immunoglobulins than serum from PKR‐deleted mice. The IgG 2A isotype significantly contributed to the increase in reactivity. Further investigation of the defect in IgG 2A expression in PKR‐deleted mice revealed that the deficit was not due to differences in the levels of IFN‐γ but involved defects in the level of T‐bet in stimulated B lymphocytes. Since T‐bet is a transcription factor for IgG 2A class switching, our data suggest that an optimal RSV‐specific IgG 2A response requires PKR through a mechanism that involves T‐bet.