The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice.

Source Publication

Journal of Immunology

Authors

Thandi M. Onami, University of Tennessee - KnoxvilleFollow
J Zeng
H. M. Joo
B. Rajini
J. P. Wrammert
M. Y. Sangster

Document Type

Article

Publication Date

April 2009

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.

Recommended Citation

Onami, Thandi M.; Zeng, J; Joo, H. M.; Rajini, B.; Wrammert, J. P.; and Sangster, M. Y., "The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice." (2009). Microbiology Publications and Other Works.
https://trace.tennessee.edu/utk_micrpubs/32