Interferon gamma signaling regulates the generation of influenza-specific memory B cells
| Autor: | Chris A Risley, Sara L Stone, Christopher D. Scharer, Jeremy M Boss, Frances E Lund |
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| Rok vydání: | 2020 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 204:171.8-171.8 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.204.supp.171.8 |
| Popis: | Memory B cells(Bmem), which can rapidly differentiate into antibody secreting cells (ASC) upon secondary challenge, are key mediators of humoral immunity. However, the signals that govern the formation and function of these cells remain poorly understood. To date, most Bmem studies have been performed with alum-adjuvanted proteins that induce type 2 immune responses. This differs significantly from the type I and II interferon (IFN) response generated after viral infection. Using a murine model of influenza, we showed that Bmem cell intrinsic expression of the IFNγ-inducible transcription factor (TF) T-bet was required for Bmem secondary ASC responses following viral challenge. Here, we demonstrate that B cell-specific deletion of the IFNγR and the IFNg-induced TF STAT1 also affects the flu-specific Bmem compartment and greatly diminishes Bmem recall responses. We demonstrate that T-bet is expressed by a subset of all flu-specific Bmem, including those expressing IgG1 and IgM receptors. Therefore, we hypothesized that T-bet expression could be used to subset the Bmem cells into those that did or did not receive prior IFNg and STAT1 programming signals. Sorting Bmem from flu-infected mice, we show that Bmem cells with the highest levels of T-bet differentiate quickly and robustly following ex vivo stimulation. By contrast, those Bmem expressing lower levels of T-bet differentiate with delayed kinetics. Taken together, these data support the notion that B cell intrinsic IFNγR signaling, mediated by STAT1, drives formation of a distinct population of T-bet expressing effector memory B cells that are programmed to rapidly differentiate following re-exposure to antigen. |
| Databáze: | OpenAIRE |
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