| First Author | Fallet B | Year | 2016 |
| Journal | Sci Immunol | Volume | 1 |
| Issue | 4 | PubMed ID | 27872905 |
| Mgi Jnum | J:259174 | Mgi Id | MGI:6142392 |
| Doi | 10.1126/sciimmunol.aah6817 | Citation | Fallet B, et al. (2016) Interferon-driven deletion of antiviral B cells at the onset of chronic infection. Sci Immunol 1(4) |
| abstractText | Inadequate antibody responses and perturbed B cell compartments represent hallmarks of persistent microbial infections, but the mechanisms whereby persisting pathogens suppress humoral immunity remain poorly defined. Using adoptive transfer experiments in the context of a chronic lymphocytic choriomeningitis virus (LCMV) infection of mice, we have documented rapid depletion of virus-specific B cells that coincided with the early type I interferon response to infection. We found that the loss of activated B cells was driven by type I interferon (IFN-I) signaling to several cell types including dendritic cells, T cells and myeloid cells. Intriguingly, this process was independent of B cell-intrinsic IFN-I sensing and resulted from biased differentiation of naive B cells into short-lived antibody-secreting cells. The ability to generate robust B cell responses was restored upon IFN-I receptor blockade or, partially, when experimentally depleting myeloid cells or the IFN-I-induced cytokines interleukin 10 and tumor necrosis factor alpha. We have termed this IFN-I-driven depletion of B cells "B cell decimation". Strategies to counter "B cell decimation" should thus help us better leverage humoral immunity in the combat against persistent microbial diseases. |
