Protective antiviral antibody responses in a mouse model of influenza virus infection require TACI
Amaya I. Wolf, … , Michael P. Cancro, Jan Erikson
Amaya I. Wolf, … , Michael P. Cancro, Jan Erikson
Published September 1, 2011
Citation Information: J Clin Invest. 2011;121(10):3954-3964. https://doi.org/10.1172/JCI57362.
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Research Article Immunology

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

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.

Authors

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

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Figure 1

Kinetics of ASCs during influenza virus infection.

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Kinetics of ASCs during influenza virus infection. (A) Naive and influen...
(A) Naive and influenza virus PR8–infected BLIMP-1–YFP mice (day 21 after infection) were analyzed for YFP+CD138+ ASCs in lung-draining medLN, lungs, and BM. Cells expressing CD4, CD8, and CD11b were excluded. Dot plots with percentages shown are representative of n = 3–5 mice from at least 2 independent experiments. (B) Level of YFP expression in ASCs from medLN, lungs and BM isolated from naive and influenza-infected BLIMP-1–YFP mice. Histograms are based on CD4–CD8–CD11b– cells and representative of n = 5–7 mice. (C) Kinetics of YFP+ ASCs during influenza virus infection. Data with mean ± SEM are representative of n = 3–5 mice per time point. (D) Immunofluorescence of lungs from naive and infected BLIMP-1–YFP mice stained for B220 (red). Original magnification, ×20, Scale bar: 100 μm.