Type-I-Interferons induce the decimation of antiviral B cells at the onset of chronic infection [nanostring]. Mus musculus

Abstract: Immune subversion represents a hallmark of persistent infection, but microbial suppression of B cell responses remains mechanistically ill-defined. Adoptive transfer experiments in a chronic viral infection model evidenced the rapid and profound decimation of B cells that responded to virus or to concomitantly administered protein. Decimation affected naïve and memory B cells and resulted from biased differentiation into short-lived antibody-secreting cells. It was driven by type I interferon (IFN-I) signaling to several cell types including dendritic cells, T cells and myeloid cells. Durable B cell responses were restored upon IFN-I receptor blockade or, partially, when depleting myeloid cells or key IFN-I-induced cytokines. Overall design: We transferred KL25HL cells (LCMV-WE-GP-specicifc B cells) into wt recipients, treated with αGR-1 (myeloid cell depletion, n=3), αIFNAR (IFN-I recpetor blockade, n=3) or control antibody (n=4), followed by rCl13 infection. Additional animals were left uninfected (n=2)). On day 3 we processed spleen and BM for low-density expression profiling of 248 inflammatory genes using the nCounter Nanostring Mouse Inflammation v2 assay (NanoString Technologies).