title: The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice.
abstract: Posttranslational modification of proteins, such as glycosylation, can impact cell signaling and function. ST6Gal I, a glycosyltransferase expressed by B cells, catalyzes the addition of alpha-2,6 sialic acid to galactose, a modification found on N-linked glycoproteins such as CD22, a negative regulator of B cell activation. We show that SNA lectin, which binds alpha-2,6 sialic acid linked to galactose, shows high binding on plasma blasts and germinal center B cells following viral infection, suggesting ST6Gal I expression remains high on activated B cells in vivo. To understand the relevance of this modification on the antiviral B cell immune response, we infected ST6Gal I(-/-) mice with influenza A/HKx31. We demonstrate that the loss of ST6Gal I expression results in similar influenza infectivity in the lung, but significantly reduced early influenza-specific IgM and IgG levels in the serum, as well as significantly reduced numbers of early viral-specific Ab-secreting cells. At later memory time points, ST6Gal I(-/-) mice show comparable numbers of IgG influenza-specific memory B cells and long-lived plasma cells, with similarly high antiviral IgG titers, with the exception of IgG2c. Finally, we adoptively transfer purified B cells from wild-type or ST6Gal I(-/-) mice into B cell-deficient (microMT(-/-)) mice. Recipient mice that received ST6Gal I(-/-) B cells demonstrated reduced influenza-specific IgM levels, but similar levels of influenza-specific IgG, compared with mice that received wild-type B cells. These data suggest that a B cell intrinsic defect partially contributes to the impaired antiviral humoral response.
authors.affiliation: Department of Microbiology, University of Tennessee, Knoxville, TN 37996, USA.
authors.forename: Junwei
authors.initials: J
authors.lastname: Zeng
authors.forename: Hye Mee
authors.initials: HM
authors.lastname: Joo
authors.forename: Bheemreddy
authors.initials: B
authors.lastname: Rajini
authors.forename: Jens P
authors.initials: JP
authors.lastname: Wrammert
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Sangster
authors.forename: Thandi M
authors.initials: TM
authors.lastname: Onami