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 Citations (Scopus)

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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Human Influenza
B-Lymphocytes
Immunoglobulin G
Antiviral Agents
N-Acetylneuraminic Acid
Galactose
Immunoglobulin M
beta-D-galactoside alpha 2-6-sialyltransferase
Germinal Center
Virus Diseases
Post Translational Protein Processing
Transferases
Plasma Cells
Glycosylation
Lectins
Glycoproteins
Lung

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice. / Zeng, Junwei; Joo, HyeMee; Rajini, Bheemreddy; Wrammert, Jens P.; Sangster, Mark Y.; Onami, Thandi M.

In: Journal of Immunology, Vol. 182, No. 8, 15.04.2009, p. 4721-4727.

Research output: Contribution to journalArticle

Zeng, Junwei ; Joo, HyeMee ; Rajini, Bheemreddy ; Wrammert, Jens P. ; Sangster, Mark Y. ; Onami, Thandi M. / The generation of influenza-specific humoral responses is impaired in ST6Gal I-deficient mice. In: Journal of Immunology. 2009 ; Vol. 182, No. 8. pp. 4721-4727.
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AU - Sangster, Mark Y.

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