IL-21 and IL-6 Are Critical for Different Aspects of B Cell Immunity and Redundantly Induce Optimal Follicular Helper CD4 T Cell (Tfh) Differentiation
| Autor: | Tania C. Escobar, Christopher Lao, Danelle Eto, Isharat Yusuf, Burton E. Barnett, Robin Kageyama, Shane Crotty, Daniel DiToro |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
B Cells
Mouse Cellular differentiation Immune Cells Immunology Plasma Cells lcsh:Medicine Biology Lymphocytic choriomeningitis Lymphocyte Activation Mice Model Organisms medicine Animals Humans lcsh:Science Antibody-Producing Cells Immunity to Infections Immune Response B cell B-Lymphocytes Multidisciplinary T follicular helper cell differentiation T Cells Interleukin-6 Interleukins T-cell receptor lcsh:R Immunity Germinal center Antiviral antibody Cell Differentiation Animal Models T-Lymphocytes Helper-Inducer medicine.disease BCL6 Germinal Center medicine.anatomical_structure Immune System Cytokines lcsh:Q Research Article Developmental Biology |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 3, p e17739 (2011) |
| ISSN: | 1932-6203 |
| Popis: | Cytokines are important modulators of lymphocytes, and both interleukin-21 (IL-21) and IL-6 have proposed roles in T follicular helper (Tfh) differentiation, and directly act on B cells. Here we investigated the absence of IL-6 alone, IL-21 alone, or the combined lack of IL-6 and IL-21 on Tfh differentiation and the development of B cell immunity in vivo. C57BL/6 or IL-21(-/-) mice were treated with a neutralizing monoclonal antibody against IL-6 throughout the course of an acute viral infection (lymphocytic choriomeningitis virus, LCMV). The combined absence of IL-6 and IL-21 resulted in reduced Tfh differentiation and reduced Bcl6 protein expression. In addition, we observed that these cytokines had a large impact on antigen-specific B cell responses. IL-6 and IL-21 collaborate in the acute T-dependent antiviral antibody response (90% loss of circulating antiviral IgG in the absence of both cytokines). In contrast, we observed reduced germinal center formation only in the absence of IL-21. Absence of IL-6 had no impact on germinal centers, and combined absence of both IL-21 and IL-6 revealed no synergistic effect on germinal center B cell development. Studying CD4 T cells in vitro, we found that high IL-21 production was not associated with high Bcl6 or CXCR5 expression. TCR stimulation of purified naïve CD4 T cells in the presence of IL-6 also did not result in Tfh differentiation, as determined by Bcl6 or CXCR5 protein expression. Cumulatively, our data indicates that optimal Tfh formation requires IL-21 and IL-6, and that cytokines alone are insufficient to drive Tfh differentiation. |
| Databáze: | OpenAIRE |
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