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

Junwei Zeng, HyeMee Joo, Bheemreddy Rajini, Jens P. Wrammert, Mark Y. Sangster, Thandi M. Onami

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Posttranslational modification of proteins, such as glycosylation, can impact cell signaling and function. ST6Gal I, a glycosyl-transferase expressed by B cells, catalyzes the addition of α-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 α-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 (μMT-/-) 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.

Original languageEnglish (US)
Pages (from-to)4721-4727
Number of pages7
JournalJournal of Immunology
Volume182
Issue number8
DOIs
StatePublished - Apr 15 2009
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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