Type-I-Interferons induce the decimation of antiviral B cells at the onset of chronic infection [RNA-seq]

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. B cell decimation represents a molecular mechanism of humoral immune subversion and reflects an unsustainable “all-in” response of B cells in IFN-I-driven inflammation. Overall design: We adoptively transferred naïve KL25HL cells (LCMV-WE-GP-specific B cells) to aIFNAR- or isotype control-treated syngeneic recipient mice, followed by rLCMV-Cl13/WE-GP. On day 3 of infection, spleen were harvested and proliferated KL25HL B cell progeny (CD45.1+B220+CFSElo) were FACS-sorted and total RNA was processed for RNAseq. n=4

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Fallet B, Narr K, Ertuna YI, Remy M, Sommerstein R, Cornille K, Kreutzfeldt M, Page N, Zimmer G, Geier F, Straub T, Pircher H, Larimore K, Greenberg PD, Merkler D, Pinschewer DD