Protective antiviral antibody responses in a mouse model of influenza virus infection require TACI

Amaya I. Wolf, Krystyna Mozdzanowska, William J. Quinn, Michele Metzgar, Katie L. Williams, Andrew J. Caton, Eric Meffre, Richard J. Bram, Loren D. Erickson, David Allman, Michael P. Cancro, Jan Erikson

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Antiviral Abs, for example those produced in response to influenza virus infection, are critical for virus neutralization and defense against secondary infection. While the half-life of Abs is short, Ab titers can last a lifetime due to a subset of the Ab-secreting cells (ASCs) that is long lived. However, the mechanisms governing ASC longevity are poorly understood. Here, we have identified a critical role for extrinsic cytokine signals in the survival of respiratory tract ASCs in a mouse model of influenza infection. Irradiation of mice at various time points after influenza virus infection markedly diminished numbers of lung ASCs, suggesting that they are short-lived and require extrinsic factors in order to persist. Neutralization of the TNF superfamily cytokines B lymphocyte stimulator (BLyS; also known as BAFF) and a proliferation-inducing ligand (APRIL) reduced numbers of antiviral ASCs in the lungs and bone marrow, whereas ASCs in the spleen and lung-draining lymph node were surprisingly unaffected. Mice deficient in transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), a receptor for BLyS and APRIL, mounted an initial antiviral B cell response similar to that generated in WT mice but failed to sustain protective Ab titers in the airways and serum, leading to increased susceptibility to secondary viral challenge. These studies highlight the importance of TACI signaling for the maintenance of ASCs and protection against influenza virus infection.

Original languageEnglish (US)
Pages (from-to)3954-3964
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number10
DOIs
StatePublished - Oct 3 2011

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Protective antiviral antibody responses in a mouse model of influenza virus infection require TACI'. Together they form a unique fingerprint.

  • Cite this

    Wolf, A. I., Mozdzanowska, K., Quinn, W. J., Metzgar, M., Williams, K. L., Caton, A. J., Meffre, E., Bram, R. J., Erickson, L. D., Allman, D., Cancro, M. P., & Erikson, J. (2011). Protective antiviral antibody responses in a mouse model of influenza virus infection require TACI. Journal of Clinical Investigation, 121(10), 3954-3964. https://doi.org/10.1172/JCI57362