A unique subset of CD11c+ B cells upregulate FasL expression in response to IL-12p40 during lethal dose influenza virus (IAV) infections.

Abstract

Abstract Our recent work has detailed a novel regulation of the IAV-specific CD8 T cell response during lethal dose IAV infections. During such infections, FasL+ plasmacytoid dendritic cells (pDC) within the regional lymph nodes (LN) target and eliminate the developing Fas+ effector CD8 T cell response limiting immunity and driving severe disease. While our studies have shown that pDC are sufficient to drive this mechanism (i.e. transfer of wild type pDC into gld mice results in elimination of activated CD8 T cells), antibody targeted elimination of pDC in wild type mice does not completely reverse CD8 T cell apoptosis. This suggested that an additional cell type might contribute to the overall loss of CD8 T cells during lethal/high pathogenic IAV infections. Here we describe a CD11c+B cell population that shares some common markers with both pDC and several defined B cell subsets, but can be distinguished from both based on unique marker expression. Our data suggests that these CD11c+ B cells are recruited to the LN in greater numbers compared to pDCs and appear to express FasL upon exposure to IL-12p40 homodimer in lethal dose IAV infections. Further our results suggest that FasL+ expression with BST2+ expression within CD11c+ B cells. Our current studies are focused on further determining the factors regulating this CD11c+B cell population and its relative contribution to the overall FasL-dependent control of the magnitude of the CD8 T cell response during lethal dose IAV infections.