The role of type I IFNs for interferon-gamma independent antiviral antibody responses 4268

Abstract Description Humoral immunity in the form of protective antibodies (Abs) serves as a critical barrier to prevent viral pathogenesis. In mice, the canonical pathway for antiviral Ab production is IFNγ-dependent. However, we have previously shown that certain inbred strains of mice produce a neutralizing antiviral Ab response in the absence of IFNγ and have genetically linked this phenotype to a single recessive locus named IFNγ-independent immunoglobulins (igii). We additionally found that the production of protective antiviral Abs in igii-resistant mice is not controlled by hematopoietic cells, but rather by the radiation resistant compartment. Previous reports have shown that type I IFN signaling in B cells can stimulate the production of antiviral Abs. To determine the role of type I IFNs in the noncanonical IFNγ-independent pathway, we generated igii-resistant mice deficient for Ifnar1 and found that type I IFN signaling is required for neutralizing antiviral Ab responses in the absence of IFNγ. However, utilizing adoptive transfer experiments, we found that type I IFN signaling in B cells is not sufficient to stimulate the production of antiviral Abs in the absence of IFNγ. Collectively, our data suggest that type I IFN signaling by stromal cells controls IFNγ-independent antiviral Ab production. Understanding the role of type I IFNs in stimulating the production of antiviral Abs will further inform our current understanding of antiviral immune responses. Funding Sources T32AI049820 Topic Categories Viral Immunology (VIR)