Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells

Mohammed Ata Ur Rasheed, Donald R. Latner, Rachael D. Aubert, Tania Gourley, Rosanne Spolski, Carl W. Davis, William A. Langley, Sang Jun Ha, Lilin Ye, Surojit Sarkar, Vandana Kalia, Bogumila T. Konieczny, Warren J. Leonard, Rafi Ahmed

Research output: Contribution to journalArticle

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Abstract

Long-lived plasma cells that reside in the bone marrow constitutively produce antibody in the absence of antigen and are the cellular basis of durable humoral immunity. The generation of these long-lived plasma cells depends upon a series of highly orchestrated interactions between antigen-specific CD4 T cells and B cells and the formation of germinal centers (GCs). In this study, we have examined the role of the cytokine interleukin-21 (IL-21) in regulating humoral immunity during acute viral infections. Using IL-21 receptor-deficient (IL-21R-/-) mice, we found that virus-specific CD4 T cells were generated after infection with lymphocytic choriomeningitis virus (LCMV) and that these CD4 T cells differentiated into T follicular helper (TFH)-like cells in the absence of IL-21 signaling. There was also no defect in the formation of GCs, although after day 15 these GCs disappeared faster in IL-21R-/- mice than in wild-type mice. Isotype switching and the initial LCMV-specific IgG response were normal in IL-21R-/- mice. However, these mice exhibited a profound defect in generating long-lived plasma cells and in sustaining antibody levels over time. Similar results were seen after infection of IL-21R-/- mice with vesicular stomatitis virus and influenza virus. Using chimeric mice containing wild-type or IL-21R-/- CD4 T cells and B cells, we showed that both B and CD4 T cells need IL-21 signaling for generating long-term humoral immunity. Taken together, our results highlight the importance of IL-21 in humoral immunity to viruses.

Original languageEnglish
Pages (from-to)7737-7746
Number of pages10
JournalJournal of Virology
Volume87
Issue number13
DOIs
Publication statusPublished - 2013 Jul 1

Fingerprint

Interleukin-21 Receptors
plasma cells
Plasma Cells
cytokines
Humoral Immunity
Cytokines
Viruses
viruses
Germinal Center
T-Lymphocytes
humoral immunity
mice
T-lymphocytes
Lymphocytic choriomeningitis virus
receptors
B-Lymphocytes
B-lymphocytes
Immunoglobulin Class Switching
CD4 Antigens
Vesicular Stomatitis

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Rasheed, M. A. U., Latner, D. R., Aubert, R. D., Gourley, T., Spolski, R., Davis, C. W., ... Ahmed, R. (2013). Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. Journal of Virology, 87(13), 7737-7746. https://doi.org/10.1128/JVI.00063-13
Rasheed, Mohammed Ata Ur ; Latner, Donald R. ; Aubert, Rachael D. ; Gourley, Tania ; Spolski, Rosanne ; Davis, Carl W. ; Langley, William A. ; Ha, Sang Jun ; Ye, Lilin ; Sarkar, Surojit ; Kalia, Vandana ; Konieczny, Bogumila T. ; Leonard, Warren J. ; Ahmed, Rafi. / Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. In: Journal of Virology. 2013 ; Vol. 87, No. 13. pp. 7737-7746.
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Rasheed, MAU, Latner, DR, Aubert, RD, Gourley, T, Spolski, R, Davis, CW, Langley, WA, Ha, SJ, Ye, L, Sarkar, S, Kalia, V, Konieczny, BT, Leonard, WJ & Ahmed, R 2013, 'Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells', Journal of Virology, vol. 87, no. 13, pp. 7737-7746. https://doi.org/10.1128/JVI.00063-13

Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. / Rasheed, Mohammed Ata Ur; Latner, Donald R.; Aubert, Rachael D.; Gourley, Tania; Spolski, Rosanne; Davis, Carl W.; Langley, William A.; Ha, Sang Jun; Ye, Lilin; Sarkar, Surojit; Kalia, Vandana; Konieczny, Bogumila T.; Leonard, Warren J.; Ahmed, Rafi.

In: Journal of Virology, Vol. 87, No. 13, 01.07.2013, p. 7737-7746.

Research output: Contribution to journalArticle

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AU - Davis, Carl W.

AU - Langley, William A.

AU - Ha, Sang Jun

AU - Ye, Lilin

AU - Sarkar, Surojit

AU - Kalia, Vandana

AU - Konieczny, Bogumila T.

AU - Leonard, Warren J.

AU - Ahmed, Rafi

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Rasheed MAU, Latner DR, Aubert RD, Gourley T, Spolski R, Davis CW et al. Interleukin-21 is a critical cytokine for the generation of virus-specific long-lived plasma cells. Journal of Virology. 2013 Jul 1;87(13):7737-7746. https://doi.org/10.1128/JVI.00063-13