title: Virally-induced upregulation of heparan sulfate on B cells via the action of type I IFN.
abstract: Cell surface heparan sulfate (HS) is an important coreceptor for many cytokines, chemokines, and growth factors. In this study, we report that splenic murine B cells express very little HS and that upon infection with either gammaherpesvirus (murine gammaherpesvirus 68) or betaherpesvirus (murine cytomegalovirus), HS is rapidly upregulated at the surface of B cells. HS upregulation was not observed in mice deficient for the type I IFN (IFN-I) receptor. Additionally, treatment of wild-type mice with the IFN-I inducer polyinosine polycytidylic acid triggered HS expression at the B cell surface. Similarly, incubation of purified splenic B cells with IFN-I, TLR ligands, or BCR stimulators ex vivo resulted in a drastic increase in HS surface expression. We found that IFN-I induced an increase in the surface expression of HS-modified syndecan 4 as well as that of an unidentified heparan sulfate proteoglycan. Finally, IFN-I treatment increased B cell responsiveness to APRIL, a cytokine involved in B cell survival and T cell-independent B cell responses. Enzymatic removal of HS from IFN-I-treated B cells inhibited APRIL. Altogether, our results indicate that upon herpesvirus infection in mice, HS is rapidly upregulated at the surface of B cells due to the action of IFN-I, potentially increasing B cell responsiveness to cytokines. Induction of HS expression at the B cell surface by stimulators of the innate immune response likely plays a key role in the development of a robust immune response.
authors: Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
authors: Nadine
authors: N
authors: Jarousse
authors: Damian L
authors: DL
authors: Trujillo
authors: Sarah
authors: S
authors: Wilcox-Adelman
authors: Laurent
authors: L
authors: Coscoy
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D002469:Cell Separation; D005434:Flow Cytometry; D018142:Gammaherpesvirinae / Q000276:immunology; D006497:Heparan Sulfate / Q000096:biosynthesis* / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology*; D047468:Immunoprecipitation; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation
chemical_list: D006497:Heparan Sulfate; D007370:Interferon Type I