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

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.

• Authors: 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
• Journal: Journal of virology (J Virol) Vol. 87 Issue 13 Pg. 7737-46 (Jul 2013) ISSN: 1098-5514 [Electronic] United States
• PMID: 23637417 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukins
• Receptors, Interleukin-21
• interleukin-21

Topics

• Animals
• Cell Differentiation (immunology)
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Germinal Center (immunology)
• Hemagglutination Tests
• Immunity, Humoral (immunology)
• Interleukins (immunology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neutralization Tests
• Plasma Cells (immunology, virology)
• Real-Time Polymerase Chain Reaction
• Receptors, Interleukin-21 (genetics)
• Virus Diseases (immunology)